Origin and Evolution of the Plague Microbe Yersinia Pestis: Molecular Genetic and Ecological Scenarios

+1-(302)-520-2644

Articles

Abstract

Introduction

Conclusion

Funding

Conflict of Interest

References

Pdf

Quick Links

Aims and scope

Indexing

Article processing charges

Editorial board

Editorial Workflow

Abstract

Introduction

Conclusion

Funding

Conflict of Interest

References

Quick Links

Aims and scope

Indexing

Article processing charges

Editorial board

Editorial Workflow

Pdf Download

Pdf View

Views 13

PDF Downloads10

Review Article | DOI: https://doi.org/10.31579/2690-4861/728

Origin and Evolution of the Plague Microbe Yersinia Pestis: Molecular Genetic and Ecological Scenarios

Victor V. Suntsov

Laboratory of Population Ecology, A.N. Severtsov Institute of Ecology and Evolution of the Russian Academy of Sciences, Moscow, Russia.

*Corresponding Author: Victor V. Suntsov, Laboratory of Population Ecology, A.N. Severtsov Institute of Ecology and Evolution of the Russian Academy of Sciences, Moscow, Russia.

Citation: Victor V. Suntsov, (2025), Origin and Evolution of the Plague Microbe Yersinia Pestis: Molecular Genetic and Ecological Scenarios, International Journal of Clinical Case Reports and Reviews, 24(3); DOI:10.31579/2690-4861/728

Copyright: © 2025, Victor V. Suntsov. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 04 March 2025 | Accepted: 14 March 2025 | Published: 17 March 2025

Keywords: yersinia pseudotuberculosis o:1b; yersinia pestis; marmota sibirica; speciation; biocenotic changes; ecological scenario; evolutionary model

Abstract

It is known that the direct ancestor of the ‘blood’ plague pathogen – the microbe Yersinia pestis – is the saprozoonotic psychrophilic causative agent of the Far Eastern scarlet-like fever (FESLF) Y. pseudotuberculosis O:1b, and the divergence of these species occurred in the recent historical past, no earlier than 30 thousand years ago in the central regions of Asia without any human involvement. These facts indicate certain changes in the habitat of a certain population (clone) of the FESLF pathogen in the region of Central Asia or adjacent regions, which caused the speciation of Y. pestis. Reconstruction of the plague microbe speciation and evolution (its phylogeny/phylogeography) is based substantially on the molecular-genetic (MG) typing of strains from the extant natural foci and fragments of ancient DNA extracted from the remains of victims of the infection. However, presented phylogenies are not congruent with facts accumulated by such classic sciences as environmental ecology (ECO), biogeography, paleontology, epizootology, etc. These contradictions require the development of an integrated methodology for studying the history of the plague pathogen, combining both the model of neutral evolution, which is the theoretical basis in the MG approach, and adaptive evolution, which is the basis of the ECO approach. Herewith an ECO phylogeny as less controversial should be used as a null hypothesis in the phylogenetics/phylogeography of Y. pestis and a factual basis for the synthesis of ECO and MG approaches to the problem of the origin and global expansion of the plague causative agent.

Introduction

Biological and taxonomic diversity of the microbe pathogens is a result of their historical development. Therefore, it is impossible to identify in detail their relationships with hosts and develop effective control techniques and procedures without insight into their evolution. Historical reconstruction of the phylogeny of causative agents is one of the priority tasks in the modern medical and biological science. At present, phylogenetic reconstructions of any taxa are inconceivable without the use of advanced molecular-genetic (MG) methodology. Meanwhile, the MG approach to the phylogenetics of pathogenic microorganisms is still too young to be considered perfect. Despite undoubtedly great achievements of this approach in diagnosing microorganisms and describing their biological diversity, its conclusions in reconstructing phylogenies are sometimes uncertain and unconvincing. In the past decades, MG approach dominated in the development of MG phylogenetics of microorganisms; however, overestimation of its achievements and underestimation of its succession are evident. The past is hidden by a thick veil of time, and all conceivable techniques, approaches and methods would be useful and necessary for the reconstruction of historical events. Comprehensive scientific experience and knowledge accumulated over the centuries are in demand. In the earliest days of phylogenetics, E. Haeckel proposed to use the method of triple parallelism for reconstruction of the animal phylogenies. The method implied consolidation of the morphological, paleontological and embryological data. Reciprocal verification of phylogenetic inferences based on the use of different approaches and methods greatly improves confidence in their reliability. Such comprehensive methodological approach is also required for the reconstruction of phylogeny of the plague causative agent. Dominating MG approach, when taken individually, still looks imperfect and not self-sufficient.
Phylogeny is a history of taxa, the roots of which in the overwhelming majority of cases have long since became extinct or are unknown. The ancestors have to be ‘figured out’ and ‘identified’ based on the characteristic traits of the extant organisms and fossils. The situation with the plague microbe Yersinia pestis is different. The latest MG data indicate that its phylogeny is inherently a reflection of the recent process of speciation and development of the extant intraspecific forms. To date, intraspecific ecological (by the main host), biochemical, genetic, and molecular diversity of the plague microbe and its various intraspecific forms (subspecies, genovariants, biovars, ecotypes, plasmidovars, etc.) have been described in sufficient detail. The fragments of ancient DNA of the plague microbe have been discovered in the remains of human victims of past pandemics. However, despite great achievements in the study of the plague microbe, the patterns of its speciation and subsequent intraspecific evolution remain obscure. The molecular characteristics of intraspecific forms say little about the strict order of their formation in time. The MG hypotheses are largely contradictory and detached from natural and historical events [1]. Meanwhile, since the time when the plague microbe was discovered about 130 years ago, a great wealth of general biological and medical knowledge has been accumulated. This available information is not only useful; in the light of new data obtained by the MG approach, it is indispensable for an appropriate reconstruction of the history of this evolutionarily young pathogen and for the improvement of the MG methodology of phylogenetic constructions.
We address the potential of reconstruction of the plague microbe phylogeny by molecular and genetic methods and show their fundamentally limited capabilities in solving this complex problem. We argue that the prospect of constructing a real phylogeny lies in the integration of ecological (sensu lato) and MG approaches. The ecological approach that we have been developing over the past 20-25 years has not yet been widely discussed in the scientific literature, so we often have to resort to self-citation and refer in the text to our early publications.
Two MG discoveries
The introduction of MG methods into bacteriology in the past two or three decades has led to two cornerstone discoveries in the problem of plague. First, the genetic analysis (study of O-antigen and conservative genes thrA, trpE, glnA, tmk, dmsA, manB) revealed an apparent direct ancestor of the plague microbe – a pseudotuberculous microbe of the 1st serotype Y. pseudotuberculosis O:1b (family Yersiniaceae/Enterobacteriaceae), a causative agent of Far East scarlet-like fever (FESLF) [2]. This intestinal pathogene is widely distributed in populations of a wide range of invertebrates and vertebrates in the cold regions of Siberia, the Far East, and Central Asia [3, 4]. Hence, the conclusion follows, that the speciation of the plague microbe from a clone of the FESLF causative agent occurred in a certain cold region of Central Asia with numerous natural foci of plague. The most likely candidate is Mongolia with its ultracontinental climate or the nearest vicinity of this country [5]. Second, contrary to the key concept of the ‘Sylvatic Plague’ theory about the great antiquity of this infection, the ‘molecular clock’ technique showed its evolutionary youth. According to molecular estimates, the causative agent of this disease emerged no earlier than 30 thousand years ago, i.e., at the turn of the Pleistocene and the Holocene or in the Holocene [6, 7]. Common evolutionary sense implies that this event was caused by environmental changes in the habitats of the FESLF causative agent. It is known that it was the last maximum Sartan cooling 22–15 thousand years ago that resulted in the most extensive climate change and notable disturbances in the North and Central Asian biocenoses. The cooling led to intensive process of speciation and development of new forms of organisms. Natural ranges of many animals and plants in Asia changed in that period. The southern border of the permafrost zone in Asia shifted almost a thousand kilometers to 42°N and reached the Gobi Desert in southern Mongolia [8]. The two aforementioned MG discoveries logically linked numerous facts from various scientific fields (ecology, biogeography, epizootology, paleontology, microbiology, paleoclimatology, etc.) and allowed development of an ecological sensu lato (ECO) scenario of the emergence and Asian expansion of a new highly pathogenic species Y. pestis, which is fundamentally different from MG scenarios [9–12].
MG phylogenies of Y. pestis
Modern phylogenies of the plague causative agent are based on the molecular approach. The most popular methodology operates with the maximum likelihood method and Bayesian analysis. In recent years, single nucleotide polymorphism (SNP) markers are more often analyzed, and the model of uniform neutral evolution is used as the basic evolutionary model (Figure 1a) [12, 13]. An important result of the MG approach is the detection of paraphyletic origin of the cluster of ‘vole’ genovariants/subspecies 0.PE (Pestoides biovar) circulating in the populations of voles (Microtina), the Siberian jerboa (Allactaga sibirica) and Mongolian pika (Ochotona pallasi pricei) in Asia [13–16]. Genovariants/subspecies of the ‘vole’ paraphyletic group 0.PE were shown to originate from an abstract most recent common ancestor (MRCA) at different times and in different geographical regions. Unfortunately, the MG approach provides no explanations for the fact that the 0.PE cluster consisting of so-called ‘non-main’ subspecies 0.PE2, 0.PE3, 0.PE4, 0.PE5, 0.PE7 and 0.PE10 formed as a paraphyletic group, whereas all other known subspecies of clusters or phylogenetic branches 0.ANT, 1.ANT, 1.IN, 1.ORI, 2.ANT, 2.MED, 3.ANT and 4.ANT were combined into a single ‘main’ subspecies Y. pestis pestis, that is, into a single monophyletic group. It is believed to originate from a single root – the population of the causative agent of plague circulating in the populations of Altai marmot (Marmota baibacina centralis) in the Tien Shan. A credible explanation for this paradox, worthy of a more thorough and comprehensive analysis, lies in the ecological approach outlined below.
Figure 1: Phylogenetic trees of Yersinia pestis: (a) – molecular genetic [13]; (b) – ecological/environmental [12] (clarifications in the text). The red arrow (Figure. 1a) shows that the cluster of marmot genovariants 0.ANT belongs to the node of polytomy N07 [17]. The dashed arrow shows the location of the polytomy node N07 on the ecological three-root tree. The dotted arrows show the location of the decomposition of genovariants/subspecies of the ‘vole’ cluster 0.PE on the ecological three-root tree. Dot arrows indicate the locations of genovariants 2.MED1 and 2.MED3 on the ecological tree. *– diversification of genovariants of the 0.ANT cluster. Phylogenetic lines of marmot subspecies/genovariants are outlined in blue.

One more important conclusion of the MG approach was the detection of a polytomy on the phylogenetic tree (N07, ‘Big Bang’). It was the starting point for phylogenetic branches 1, 2, 3 and 4 on the eve of the supposed second pandemic (‘Black Death’, 1346). That is, it was shown that a host of natural plague foci formed almost simultaneously (star-shaped) in the populations of marmots, ground squirrels and gerbils in the vast areas of Central Asia and Tibet. Moreover, three different subbranches/genovariants 2.ANT3, 3.ANT2 and 4.ANT1 formed in populations of one host species, the Mongolian marmot (Marmota sibirica). The MG approach fails to reveal or even hypothesize the reason for diversity of the plague causative agent at the level of subbranches/genovariants in Mongolian marmot populations. This phenomenon has a credible ecological explanation. Meanwhile, MG phylogenies demonstrate a number of significant inconsistencies and contradictions with ‘non-molecular’ facts, which cast doubt on ‘molecular’ conclusions in general (Figure 1a,b).
First, the MG approach proclaims a two-stage Asian expansion of the causative agent from the supposed center of speciation (Tibet? Caucasus? Altai? Angola? East Africa?) and the initial formation of the primary range of exclusively ‘vole’ plague foci in Asia. This range encompassed vast territories from northeastern China and eastern Tibet in the east to the Caucasus in the west and, possibly, to Angola, where the ‘non-main’ subspecies 0.PE3 Y. pestis angolica was found [18]. ‘Plague-like’ causative agent in the ‘vole’ foci exhibits selective virulence and, in some MG and biochemical properties, is close to its pseudotuberculous ancestor. According to the MG version, on the eve of the first pandemic (‘Plague of Justinian’, 576 AD), a causative agent of the ‘vole’ subspecies 0.PE5 Y. pestis ulegeica that forms natural foci in populations of the Mongolian pika in the Mongolian Altai and the Altai Mountains in Russia, under unknown circumstances penetrated from Mongolia into the Altai marmot population in the Tien Shan. The subspecies developed there in a highly virulent ‘marmot’ biovar Antiqua (genovariant/subspecies 0.ANT1, 0.ANT2, 0.ANT3 and 0.ANT5). Later, following the MG logic, the causative agent of the real ‘marmot’ plague from the Tien Shan spread in a second wave within the former ‘vole’ range in Asia and dispersed across the northern Caspian region, the Middle East and Hindustan [14]. Such a two-stage pattern of expansion of plague within the Asian range does not fit the epizootological concept of the spread of a causative agent from the area of speciation according to the principle of ‘spreading of an oil stain on the paper’ [19].
Second, the crucial drawback of the present-day MG approach is its limited ability to identify the original host of the plague causative agent solely by statistical methods. Identifying the original host of the plague pathogen is the key to understanding its history. Knowledge of the original host makes it possible to reconstruct its history at the population-species level without resorting to complex MG computational statistical technology. To date, the genetic and nucleotide structures of the causative agent from the majority of natural foci known in the world have been studied. Its most ancient genovariants/subspecies have been identified. However, MG methods do not allow us to indicate populations of the particular rodent species in which the original population of the plague microbe was formed. The MG approach reconstructs only the emergence of the abstract common ancestor (MRCA) of Y. pestis from the FESLF clone. Neither its host environment, nor population characteristics are discussed. A featureless MRCA is characterized only statistically by marker traits that are not determined by ecological functions. At the same time, it is indisputable that new species originate in the bowels of ancestral populations, so the MRCA must represent a certain original subspecies or genovariant of the plague microbe. But for now it is still unclear whether MRCA should be classified as a mature species and initial subspecies of Y. pestis, or a transitional nameless form Y. pseudotuberculosis/pestis. The MG approach clearly indicates the ancestral species (unfortunately, not its specific original population/subspecies) on the phylogenetic tree of Y. pestis. However, it fails to reveal any unique features of the population-genetic speciation process and, main, to specify the original host of the plague microbe. In this case, the MG approach cannot be considered self-sufficient for a reliable reconstruction of the history of the plague causative agent, and the model of neutral evolution seems to be not reliable for the reconstruction of its phylogeny.
Third, the MG approach in phylogenetics of the plague microbe has two components: molecular and genetic. These components are not in harmony with each other, they are alternative and antagonistic. Molecular methodology operates with ‘phylogenetic’ nucleotide markers designated as evolutionarily neutral. ‘Neutral’ model of evolution characterizes the gradual transformation of a taxon under the impact of genetic drift. Analysis of the chosen neutral characters determines the topology of the phylogenetic tree of Y. pestis. At the same time, the genetic methodology operates with ‘adaptive’ traits: the plague microbe has acquired specific factors of virulence, transmission and communication; these factors are encoded by particular genes and gene complexes [20]. Moreover, the genetic approach to Y. pestis phylogenetics proclaims acquisition of specific properties during the ‘saltation evolution’. This evolutionary process implies the horizontal transfer of genes, primarily those of the virulence plasmids pFra and pPst, from the environment or from other microorganisms, as well as single-act deletions and inactivations/pseudogenizations of gene structures that have lost their functions in a new environment [21, 22]. The question is why revolutionary adaptive genetic changes in the plague microbe, which determined its history, are not reflected in the topology of the phylogenetic tree. If we follow the evolutionary logic, the analysis of ‘phylogenetic’ and ‘adaptive’ traits used in reconstruction of Y. pestis phylogeny requires coordination in methodology. Reconstruction of the history of the ‘young’ causative agent of plague should not be restricted to the analysis of only neutral nucleotide ‘phylogenetic’ traits. ‘Adaptive’ features are more indicative in this case; they should be definitely used or even play the main role in the construction of the phylogenetic tree topology.
‘Ancient’ plague foci
Fossil taxa potentially play a key role in reconstructing the history of studied phylogenetic groups, as they represent the roots and early branches of phylogenetic trees. ‘Fossil (archaeological) taxa’ and ‘ancient’ plague foci of Y. pestis are reconstructed from DNA fragments extracted from the remains of human victims of the first and second pandemics and materials found in the earlier burial sites [23–25]. Since some DNA fragments discovered in Europe are close in their nucleotide structure to homologous fragments of pseudotuberculous microbe, the ‘archaeological’ taxa/subspecies Gok2, LNBA and other proposed on the basis of these fragments are placed at the root of phylogenetic trees of Y. pestis. No modern genotypes of the plague microbe with molecular markers homologous to ‘archaeological’ ones have been found, and the ‘archaeological’ taxa/subspecies are considered extinct. However, no environmental conditions convenient for the natural foci of plague are known for post-glacial Europe in the Holocene. The region was lacking arid landscapes populated by numerous burrowing rodents, which were massively parasitized by fleas [26]. Numerous original natural foci were confined to the vast arid Sahara-Gobi zone, but that zone did not stretch into Europe. Therefore, no sound ecological and epizootological grounds can support any natural lineages in the phylogeny of the plague microbe, which became extinct after extinction of the hosts or vectors of the pathogene. The extinct foci of plague in Europe were undoubtedly synanthropic. They had anthropogenic (imported) origin and were most likely supported by stable extant subspecies of the causative agent [26].
Imperfection of the MG-approach
The MG approach to the reconstruction of the history of the plague pathogen relies on the theory of neutral evolution and the corresponding phylogenetic methodology as a theoretical basis. However, the causative agent of plague is unique in the genus Yersinia and the family Yersiniaceae, which combine pathogens of intestinal infections: plague is the only vector-borne infection in these taxa. The unique origin and evolution of the plague pathogen are largely characterized by adaptive (not neutral!) traits: it is the adaptive traits that most clearly characterize the history of the plague microbe. Accordingly, the evolutionary model, along with neutral ones, should provide for adaptive processes, and in phylogenetic reconstructions in addition to molecular and genetic characteristics, should also use ecological (adaptive) ones. In addition, in the problem of reconstructing the history of the plague microbe the methods of analysis widely accepted in molecular phylogenetics do not quite correspond to the object of research. It is known that the causative agent of FESLF is a direct ancestor of plague microbe, and that the approximate time of divergence of plague and pseudotuberculosis microbe is no earlier than 30 thousand years ago. That is, speciation and intraspecific divergence of the plague pathogen took place in the recent evolutionary and historical past in an (almost) modern biogeocenotic environment, in an environment that has an (almost) modern appearance, when modern species and subspecies of rodents-hosts and fleas-vectors of the plague microbe and arid landscapes within (almost) modern their boundaries already existed. In this case, the reconstruction of the history of the plague pathogen is to a greater extent a problem not of phylogenetics, but of phylogeography, which, in addition to molecular and genetic concepts, operates with such ecological concepts as subspecies, geographical population, range, territorial expansion, direct relatedness, gene flow, and many others. From the point of view of the ecological approach, summarized below, some of the methods of the MG approach for solving the history of plague seem to be not fully justified. For example, the CO92 strain isolated from a sick person infected from a domestic cat in the United States is chosen as a reference for ‘calculating’ the degree of kinship of all the studied genovariants/subspecies of the plague microbe, or the strain YP32953 Y. pseudotuberculosis O:1b isolated in France from a sick patient is used as an outgroup (nearest-neighbor) to characterize the root phylogenetic tree. These strains had a long anthropogenic history, not without human participation they got to the United States and France. As a reference strain and a representative of the outgroup, it is more reliable to select strains from wild rodent populations living in Central Asia, the most likely area of origin of plague) [5, 11, 12, 19].
Mongolian marmot is an original host of plague
In case the plague microbe has emerged recently in an almost modern biogeocenoses, an ecological, i.e., adaptationist approach is of particular value for phylogenetic/phylogeographic reconstructions. It provides for a more complete narrative of the history of the plague microbe, rich in biological information. Actually, the reconstruction of speciation processes and intraspecific diversification of the plague causative agent is the prerogative of phylogeography, the methodology of which operates with such concepts as speciation, intraspecific diversification, subspecies, geographic population, range, ecological subniche and migration.
Identification of the original host of the plague causative agent is a cornerstone problem in the reconstruction of its history. It allows matching the significance of ‘adaptive’ (ecological, biochemical, genetic) and neutral ‘phylogenetic’ (IS, VNTR, CRISPR, SNP, etc.) traits/markers in the reconstruction of the evolutionary history of the plague microbe and opens up broad prospects for studies of the patterns of molecular evolution in general. If the real ancestor and the original form of the plague microbe are known, monophyletic groups could be accurately assembled in accordance with the adaptive characteristics and on the basis of biogeographical distribution of the main hosts of the causative agent.
Any speciation process is caused by changes in the habitat of the original population. Consequently, the recent transformation of the clone of the FESLF causative agent into the original population of the plague microbe was caused by a change in its habitat, which led to modification of its life cycle. Causative agent of FESLF inhabits both the external organic matter (the soil, excrements and animal remains) and the digestive tract of a wide range of invertebrates and vertebrates. The habitats of the plague causative agent are the organisms of a rodent (host) and a flea (vector). The key evolutionary event in the genesis of the plague microbe as a new species was the development of the following factors ensuring continuous circulation of the plague microbe: the virulence to the rodent host on the part of the microbe, the immunity to the microbe on the part of the rodent host, and transmission by fleas. In the unanimous opinion of experts, this event occurred in populations of a certain rodent species. A cornerstone issue is the identity of the species. According to unsubstantiated MG versions, the pathogene could be originally hosted by the Nile grass rat Arvicanthis niloticus [27], the Siberian jerboa Allactaga sibirica [13], the Common vole Microtus arvalis [28] and marmots, most likely the Altai marmot [29–31]. However, ecological data definitely indicate that the plague microbe was initially hosted by the Mongolian marmot. No other sufficiently deeply substantiated options have been proposed in the world scientific literature. Therefore, this presumption should be accepted as a null hypothesis for studying the history of plague and its causative agent until new, more substantiated variants of the main host appear.
We argue that the original habitat of the plague microbe was the parasitic system of the Mongolian marmot and the flea Oropsylla silantiewi. A shift of the FESLF causative agent to a new ecological niche and speciation of the plague microbe could have occurred no earlier than 30 thousand years ago. These events were caused by changes in the aforementioned parasitic system under the influence of particular abiotic and/or biotic factors, which needs to be discussed.
The internal environment of homoiothermic animals is regulated by homeostasis mechanisms and remains highly stable. Therefore, there is no reason to believe that in the past 30 thousand years physiological, biochemical and other characteristics of the intestinal habitat of the pseudotuberculous microbe in the body of homoiothermic hosts, including the Mongolian marmot, have undergone any radical changes. In addition, it is necessary to understand why the plague pathogen turned out to be a unique representative of the intestinal microbial family Yersiniaceae/ Enterobacteriaceae? This is the only representative of the family among hundreds that is transmitted not by the traditional alimentary route, but by a transmissible way through flea bites. The question arises: what happened in the nature of Central Asia (or nearest regions) in the recent historical past, which led to the evolutionary transition of the intestinal pathogen into the ‘blood’ of rodents? No causes and mechanisms have been revealed that in the not-too-distant past could have led to colonization of the lymphomyeloid complex of homoiothermic hosts by pseudotuberculous microbes and transmission by overcoming the intestinal epithelial barrier. Therefore, it seems reasonable to accept the alternative that the evolutionary transition of the pseudotuberculous microbe from the digestive tract into the lymphomyeloid complex of the Mongolian marmot was initiated by some external rather then host-dependent factors. According to the ECO scenario, these were two abiotic factors that arose at different times: the aridity and severity of the climate in Central Asia [9–12, 32–34]. The arid climate of Central Asia that gave rise to the development of the species-specific behavior of the Mongolian marmot could be considered a remote abiotic cause. The Mongolian marmot inhabiting arid steppe and mountain-steppe landscapes of Central Asia is the only species that exhibits specific protective behavior. It plugs its wintering burrow with stones and fine soil mixed with its own excrements as a binding material. When building such a plug, a marmot transports construction materials from the toilet chamber in its teeth, and a large amount of excrements together with the FESLF causative agent ends up in the animal’s mouth cavity. It results in extensive accumulation of the causative agent of FESLF in the marmot’s mouth cavity before it gets ready for hibernation. Marmots stop feeding prior to and during hibernation, so the FESLF causative agent does not enter their gastrointestinal tract in this period and the infection process does not develop in hibernating animals. In active marmots, pseudotuberculosis infection proceeds, presumably, like in other mammals.
The Sartan cooling is a trigger for Y. pestis speciation
The accumulation of the FESLF causative agent in the mouth cavity of the Mongolian marmot during hibernation was only a remote prerequisite for speciation of the plague microbe. The actual trigger for the speciation process was the last maximum Sartan cooling in Asia at the Pleistocene-Holocene boundary 22–15 thousand years ago. Within the range of the Mongolian marmot in Mongolia, the maximum cooling resulted in freezing of the soil to the depth of two meters and even deeper [8], which altered the behavior of larvae of the marmot flea O. silantiewi. Under normal conditions, flea larvae feed on detritus in the marmot underground nests. However, with the onset of maximum cooling and consequent deep freezing of the soil, flea larvae shifted to feeding on the blood of dormant hosts in winter and spring. Such a behaviour is still observed in larvae in Southern Siberia and Central Asia nowadays. Hematophagy of marmot flea larvae is not a crucial adaptation; this temporary phenomenon is timed to the cold season and caused by the positive thermotaxis, a primitive behavioral reaction. In winter, the ground freezes to the depth of the hibernation nest chambers of the Mongolian marmot (2–3 m). The flea larvae move from the frozen nest lining to the warmer bodies of dormant animals (the body temperature of a marmot in a torpor state is about 5°C). The larvae stochastically get from marmot’s fur into its mouth cavity, where they injure the mucous lining and feed on oozing blood (facultative hematophagy of flea larvae is often found in fleas of various species that parasitize warm-blooded animals living in cold areas of the world [10]). Thus, facultative behavior of marmot fleas enabled the causative agent of FESLF to penetrate via a traumatic route from the mouth cavity of dormant marmots directly into the blood and cause trivial ‘blood poisoning’ on a population-wide scale. A unique traumatic pathway of FESLF infection in populations of the Mongolian marmot resulted in rapid ‘quantum’ translocation of the intestinal pathogene to a new ecological niche, the lymphomyeloid system of the Mongolian marmot, and its transformation into the plague causative agent Y. pestis [33] (Figure 2).
Figure 2: A shift of the Yersinia pseudotuberculosis 0:1b clone to the new ecological niche. The source of FESLF traumatic infection of the Mongolian marmot during hibernation was the excrements, which is accumulated in the toilet chambers in wintering burrows and used to make a burrow ‘plug’ [8, 9]. Body temperature of marmots: in torpor 5оС, in euthermic states 37оС.
Parapatric speciation of the plague causative agent
If the traits of the original host populations in which the intestinal causative agent of FESLF transformed into a blood parasite are known and the evolutionary youth of the plague microbe, as well as its coexistence with a direct ancestor, is considered, the evolutionary history of the plague causative agent can be adequately reconstructed with the use of ecological (sensu lato) methods. The range of the Mongolian marmot in Central Asia is formed by three relatively independent geographical populations. Subspecies M. sibirica sibirica occurs in the Khentei Mountains in eastern Mongolia, Barga and on the western slopes of the Khingan Ridge in northeastern China. M. sibirica caliginosus live on Khangai Highlands in Central Mongolia. M. sibirica ssp., a subspecies not yet described, inhabits the Kharhiraa-Turgen-Mongun-Taiga mountain complex in Tyva and western Mongolia. The Sartan cooling encompassed the entire Central Asia and the plague microbe Y. pestis could be assumed to arise as a species almost simultaneously in three geographical populations of the Mongolian marmot, which gave rise to three geographical populations (subspecies, genovariants) of the pathogene: 2.ANT3 (Khentei, Khingan, Barga), 3.ANT2 (Khangai) and 4.ANT1 (Kharhiraa-Turgen-Mongun-Taiga) [11, 12]. Therefore, the origination of Y. pestis species from three isolated populations of the FESLF causative agent should be considered parapatric (peripatric?) speciation, whereas the ‘explosive’ emergence of genovariants/subspecies 2. ANT3, 3.ANT2 and 4.ANT1 in populations of the Mongolian marmot is reflected in the molecular phylogenies as a node of polytomy N07 (‘Big Bang’) (Figure 1, 3A,B).
Further territorial expansion and host specialization followed independent routes (Figure 3A). As a consequence, Y. pestis represents a paraphyletic group of three holophyletic independent groups, rather than a single monophyletic group of taxa (subspecies). Similarity of three holophyletic groups in the nucleotide markers is associated with parallelisms that arose during the one-way evolution of vicariating populations under (almost) identical conditions. In N07 node, the derivatives of the ‘gerbil-gopher’ genovariants 2.MED1 and 2.MED3 do not form a single monophyletic branch of 2.MED, but are included in different holophyletic groups 2.ANT3 and 4.ANT1 (Figure 1).The homoplastic similarity of holophyletic groups, but not their direct kinship, predetermines the need for a unique ad hoc model of the evolution of the analyzed molecular characters.

Figure 3: (a). Development of three genovariants/subspecies of Yersinia pestis (2.ANT3, 3.ANT2 and 4.ANT1) in three geographical populations of the Mongolian marmot Marmota sibirica sibirica (Khentei, Khingan, Barga), M. sibirica caliginosus (Khangai) and M. sibirica ssp. (Kharhiraa-Turgen-Mongun-Taiga), respectively, and independent routes of its territorial expansion. 1 – the range of the Mongolian marmot; 2 – regions of origination of Y. pestis subspecies; 3 – ways of expansion of original subspecies; 4 – ways of expansion of derived subspecies; 5 – natural plague foci in China, according to [35]. The dots-line indicate southern boundary of permafrost and the boundary of the Sartan cooling. (b). Family ties of the causative agents of pseudotuberculosis and plague. The relatedness of the 2.ANT3, 3.ANT2 and 4.ANT1 subspecies of the plague microbe from different geographical populations of the Mongolian marmot is mediated by different pseudotuberculous ancestors distributed in Khentei (FESLFa), Khangai (FESLFb) and the Kharhira-Turgen mountain range (FESLFc).

Conclusion

Awareness of the nature of the direct ancestor of the plague microbe (intestinal causative agent of FESLF) and the original host (the Mongolian marmot), a well-established divergence from the ancestor in the recent geological past, and the unique position of the ‘blood’ plague microbe among the intestinal inhabitants of the family Yersiniaceae (Enterobacteriaceae) allow us to base the topology of the Y. pestis phylogenetic tree on ecological and biogeographical data. Complex molecular statistical calculations of the historical trajectories of the pathogen, which are redundant in this unique case, can be avoided. Ecological evidence suggests rapid ‘quantum’ speciation of the plague microbe in three geographic populations of the Mongolian marmot. The transition of original subspecies 2.ANT3, 3.ANT2 and 4.ANT1 from populations of the Mongolian marmot to sympatric, semisimpatric and/or adjoining populations of other host species (the Daurian and long-tailed ground squirrels, Mongolian gerbil, Brandt vole, Mongolian pika, Altai marmot) accompanied by transformation into different genovariants fit the principle of ‘spreading of an oil stain on the paper’. Adaptation to new hosts led to differentiation of new microbial subspecies.
The topology of Y. pestis phylogenetic tree proposed by the ecological approach, is fundamentally different from topologies derived from the results of molecular studies. But the history of the plague microbe is invariant. Harmonization of ECO and MG methodologies should be an immediate task of phylogenetic studies of the plague causative agent. The MG approach considers a model of neutral uniform evolution as an evolutionary model. The comparison of SNP traits (or other molecular characters) of all studied intraspecific forms (genovariants, subspecies) of the plague microbe and the ancestral causative agent of FESLF is based on a unified algorithm. However, the speciation and expansion of the plague microbe are essentially different processes. Speciation is a ‘quantum’ population genetic process with the shift of the evolving group (taxon) to a fundamentally different ecological niche and adaptive zone. This process had a macroevolutionary effect. The newly formed species was assigned the taxonomic status of a new species Y. pestis in the family Yersiniaceae (Enterobacteriaceae), but this new species is worthy of the status of a new family of ‘blood parasites’. Expansion is a gradual microevolutionary process with frequent bottleneck effects arising when the pathogene shifts to a new host. Since the macro- and microevolutionary processes in the history of the plague microbe are not identical, the basic model of evolution of characteristic traits in phylogenetic constructions should be an ad hoc model. It should somehow simultaneously reflect various aspects of the evolutionary process: neutral and adaptive, gradual and quantum, macro- and microevolutionary. The prospects for the development of such a combinatorial model are a function of the progress in integration of the achievements of molecular genetic and ecological approaches.

Funding

No funding was used.
Ethics approval and consent to participate.
This work does not contain any studies involving human and animal subjects.

Conflict of Interest

The author of this work declares that he has no conflicts of interest.

References

Suntsov VV (2024). Uniqueness and Phylogenesis of the Plague Microbe Yersinia pestis. Biology Bulletin 51(6) 1505-1514.
View at Publisher | View at Google Scholar

Skurnik M, Peippo A and Ervela E (2000). Characterization of the O-antigen gene cluster of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b. Molecular Microbiology 37(2) 316-330.
View at Publisher | View at Google Scholar

Somov GP (1979). Far East Scarlet-like Fever. Moscow: Medicina (in Rus).
View at Publisher | View at Google Scholar

Fukushima H, Matsuda Y, Seki R, et al. (2001). Geographical Heterogeneity between Far Eastern and Western Countries in Prevalence of the Virulence Plasmid, the Superantigen Yersinia pseudotuberculosis-Derived Mitogen, and the High-Pathogenicity Island among Yersinia pseudotuberculosis Strains. Journal of Clinical Microbiology 39(10) 3541-3547.
View at Publisher | View at Google Scholar

Suntsov VV (2022). Climate Changes in Central Asia as a Prerequisite and Trigger of Plague Microbe (Yersinia pestis) Speciation. Contemporary Problems of Ecology 15(4) 373-382.
View at Publisher | View at Google Scholar

Achtman M, Morelli G, Zhu P, et al. (2004). Microevolution and history of the plague bacillus, Yersinia pestis. Proceedings of the National Academy of Sciences 101(51) 17837-17842.
View at Publisher | View at Google Scholar

Morelli G, Song Y, Mazzoni CJ, et al. (2010). Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nature Genetic 42(12) 1140-1143.
View at Publisher | View at Google Scholar

Owen LA, Richards B, Rhodes EJ, et al. (1998). Relict permafrost structures in the Gobi of Mongolia: Age and significance. Journal of Quaternary Science 6 539-547.
View at Publisher | View at Google Scholar

Suntsov VV and Suntsova NI (2000). Ecological Aspects of Evolution of the Plague Microbe Yersinia pestis and the Genesis of Natural Foci. Biology Bulletin 27(6) 541-552.
View at Publisher | View at Google Scholar

Suntsov VV and Suntsova NI (2006). Plague. Origin and Evolution of Epizootological system (ecological, geographical and social aspects). Moscow: KMK Scientific Press (in Rus).
View at Publisher | View at Google Scholar

Suntsov VV (2021). Host Aspect of Territorial Expansion of the Plague Microbe Yersinia pestis from the Populations of the Tarbagan Marmot (Marmota sibirica). Biology Bulletin 8 211-223.
View at Publisher | View at Google Scholar

Suntsov VV (2022). Polytopic Speciation of the Plague Microbe Yersinia pestis as the Cause of the trichotomy in the Geographic Populations of the Mongolian Tarbagan Marmot (Marmota sibirica). Biology Bulletin Reviews 12(5) 504–515. https://doi: 10.1134/S2079086422050085
View at Publisher | View at Google Scholar

Cui Y, Yu C, Yan Y, Li D, et al. (2013). Historical variations in mutation rate in an epidemic pathogen. Yersinia pestis. Proceedings of the National Academy of Sciences 110(2) 577–582. https://doi/10.1073/pnas.1205750110
View at Publisher | View at Google Scholar

Demeure CE, Dussurget O, Fiol GM, Guern A-SL, Savin C and Pizarro-Cerda J (2019). Yersinia pestis and plague: An updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics. Genes and Immunity 20(5) 357-370.
View at Publisher | View at Google Scholar

Kislichkina AA, Platonov ME, Vagaiskaya AS, et al. (2019). Rational taxonomy of Yersinia pestis. Mololecular Genetic, Microbiology and Virology 34 (2) 110-117 (in Rus).
View at Publisher | View at Google Scholar

Kutyrev VV, Eroshenko GA, Motin VL, et al. (2018). Phylogeny and classification of Yersinia pestis through the lens of strains from the plague foci of Commonwealth of Independent States. Frontiers in Microbiology 9 Art. 1106.
View at Publisher | View at Google Scholar

Wu Y, Hao T, Qian X, et al. (2022). Small Insertions and Deletions Drive Genomic Plasticity during Adaptive Evolution of Yersinia pestis. Microbiology Spectrum 10(3) e0224221.
View at Publisher | View at Google Scholar

Eppinger M., Worsham PL, Nikolich MP, et al. (2010). Genome Sequence of the Deep-Rooted Yersinia pestis Strain Angola Reveals New Insights into the Evolution and Pangenome of the Plague Bacterium. J. Baceriology 192(6) 1685-1699.
View at Publisher | View at Google Scholar

Suntsov VV (2023). Molecular phylogenies of the plague microbe Yersinia pestis: an environmental assessment. AIMS Microbiology 9(4) 712-723.
View at Publisher | View at Google Scholar

Suntsov VV (2021). Genomogenesis of the Plague Bacteria Yersinia pestis as a Process of Mosaic Evolution. Russian Journal of Genetics 57(2) 139-151.
View at Publisher | View at Google Scholar

Sun Y-C, Jarrett CO, Bosio CF and Hinnebusch BJ (2014). Retracing the Evolutionary Path that Led to Flea-Borne Transmission of Yersinia pestis. Cell Host & Microbe 15 578-586.
View at Publisher | View at Google Scholar

Hinnebusch BJ, Chouikha I and Sun Y-C (2016). Ecological Opportunity, Evolution, and the Emergence of Flea-Borne Plague. Infection and Immunity 84(7) 1932-1940.
View at Publisher | View at Google Scholar

Bos KI, Herbig A, Sahl J, et al. (2016). Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus. eLife 5 e12994.
View at Publisher | View at Google Scholar

Valtuena AA, Neumann GU, Spyrou MA, et al. (2022). Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague. Proceedings of the National Academy of Sciences 119(17) e2116722119. https://doi.org/10.1073/pnas.2116722119
View at Publisher | View at Google Scholar

Eaton K., Featherstone L., Duchene S., et al. (2023). Plagued by a cryptic clock: insight and issues from the global phylogeny of Yersinia pestis. Communications Biology 6(23).
View at Publisher | View at Google Scholar

Stenseth NC, Taoc Y, Zhang C, et al. (2022). No evidence for persistent natural plague reservoirs in historical and modern Europe. Proceedings of the National Academy of Sciences 119(51) e2209816119.
View at Publisher | View at Google Scholar

Achtman M, Zurth K, Morelli G, et al. (1999). Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proceedings of the National Academy of Sciences 96(24) 14043-14048.
View at Publisher | View at Google Scholar

Pisarenko SV, Evchenko AYu, Kovalev DA, et al. (2021). Yersinia pestis strains isolated in natural plague foci of Caucasus and Transcaucasia in the context of the global evolution of species. Genomics 113(4) 1952–1961.
View at Publisher | View at Google Scholar

Devignat R (1951). Varietes de l’espece Pasteurella pestis. Nouvelle hypothese. Bulletin of World Health Organization 4(2) 242-263.
View at Publisher | View at Google Scholar

Wang X, Zhou D, Qin L, et al. (2006). Genomic comparison of Yersinia pestis and Yersinia pseudotuberculosis by combination of suppression subtractive hybridization and DNA microarray. Archives of Microbiology 186 151-159.
View at Publisher | View at Google Scholar

Anisimov NV, Kislichkina AA, Platonov ME, et al. (2016). On the origin of hypervirulence of the causative agent of the plague. Medical Parazitology and Parasite Diseases 1 36–42 (in Rus).
View at Publisher | View at Google Scholar

Suntsov VV (2018). The exceptional role of the specific marmot flea Oropsylla silantiewi (Ceratophyllidae: Siphonaptera) in the speciation of the causative agent of the plague – the microbe Yersinia pestis. Parasitologia 52(1) 3–18 (in Rus).
View at Publisher | View at Google Scholar

Suntsov VV (2018). Quantum Speciation of Yersinia pestis Plague Microbe in a Heteroimmune Environment: In the Populations of Hibernating Tarbagan Marmots (Marmota sibirica). Contemporary Problems of Ecology 11 343-354.
View at Publisher | View at Google Scholar

Suntsov VV (2022). Phylogenesis of the Plague Microbe Yersinia pestis: The Uniqueness of the Evolutionary Model. Herald Russian Academy of Science 92(5) 609-616.
View at Publisher | View at Google Scholar

Zhou D., Han Y., Song Y., et al. (2004). Comparative and evolutionary genomics of Yersinia pestis. Microbes and Infection 6 1226-1234.
View at Publisher | View at Google Scholar

We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.

Dr David Vinyes

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

Luiz Sellmann

I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.

Zhao Jia

Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."

Thomas Urban

I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.

Cristina Berriozabal

To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.

Dr Tewodros Kassahun Tarekegn

"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".

Dr Shweta Tiwari

I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.

Dr Farooq Wandroo

Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.

Dr Anyuta Ivanova

We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.

Dr David Vinyes

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

Virginia E. Koenig

Quick Links

Home

Explore Journals

Open Access

Authors

Editors

About Us

Submit Manuscript

Explore Journals

Article Processing Charges

Peer Review at Auctores

Submission Guidelines

News letter

Get latest update, news & journal offers

Subscribe!

Contact

AUCTORES PUBLISHING LLC,
16192 Coastal Highway, Lewes , DE 19958, USA
Phone: +1-(302)-520-2644
Email: info@auctorespublishing.com

Contact Us (We contact you)

© 2017-2025 Auctores Online, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use. Creative Commons License Open Access by Auctores Online is licensed under a Creative Commons Attribution 4.0 International License.