AUCTORES
Globalize your Research
Review Article | DOI: https://doi.org/10.31579/2690-8808/237
1Medical microbiology department /College of Health Sciences/ Hawler Medical University, Erbil/Iraq
2Microbiology, Education College, Salahaddin University, Erbil, Kurdistan, Iraq.
*Corresponding Author: Fattma A. Ali. College of Health Sciences/ Hawler Medical University, Erbil/Iraq.
Citation: Fattma A. Ali, Ahmed Akil Al-Daoody, Cheman H. Hamid, Sawsan M. Sorche, (2024), The Role of Virulence Factors of Haemophilus Influenza, J, Clinical Case Reports and Studies, 6(1); DOI:10.31579/2690-8808/237
Copyright: ©, 2024, Fattma A. Ali. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 11 December 2024 | Accepted: 30 December 2024 | Published: 03 January 2025
Keywords: haemophilus influenza; virulence factors; pathogenesis; unencapsulated; encapsulated
Background: Haemophilus influenzae is a pathogenic bacterium that frequently leads to serious infections, especially in newborns. Haemophilus influenzae is a Gram-ve coccobacillus belonging to the Pasteurellaceae family. It is microscopic in size, ranging from 0.3 to 1 micrometers. Its facultative anaerobic can survive with or without oxygen and has the ability to change its shape. It grows in an environment with increased levels of carbon dioxide. The development of this organism on chocolate agar is facilitated by a medium that contains two erythrocyte factors: factor X (hematin) and factor V (phosphopyridine nucleotide).
Objectives: Our study aimed to carry out the role of the virulence factors of haemophilus influenza that facilitate the pathogenesis of infections caused by this bacteria.
Main body: The pathogenicity determinants of H..influenzae contribute to its capacity to colonies and induce illness in the host. The following are important virulence.factors of H.. influenzae: Capsule used for inhibition of phagocytosis to avoid detection by the host's immune system. Pili: are adhesion molecules that enable the binding of cells or microorganisms to surfaces. IgA Protease: H..influenzae secretes IgA1 protease, an enzyme that specifically splits human IgA1 antibodies. Endotoxin (Lipopolysaccharide - LPS) This endotoxin has the ability to initiate an inflammatory reaction in the host. Beta- lactamase: Beta-lactamase is a bacterial enzyme that provides resistance to beta-lactam antibiotics.
Conclusion: H. influenzae can be categorised into six separate categories, known as serotypes a, b, c, d, e, and f, based on the presence of a polysaccharide capsule. Types A, E, and F are also isolated, although less frequently than type B. C and D are hardly identified. All serotypes, especially type b, are frequently responsible for lower respiratory tract infections, such as pneumonia. In addition, they have the potential to induce various additional severe illnesses including meninigitis , epiglottitis, cellulitis , septic arthritis and bacteremia.
Haemophilus influenzae is a pathogenic bacterium that frequently leads to seriousinfections, especially in newborns. Richard. Pfeiffer originally documented it in 1892. Throughout an influenza outbreak, he discovered the presence of H. influenzae in the sputum of patientsand put up a hypothesis suggesting a direct link between this bacteria and the clinical illness often referred to asinfluenza. The organismwas given the name Haemophilus by Charles-Edward Winslow, et al. in 1920. The discovery that influenza is caused by a virus and that H. influenzae can induce secondary infection was made in 1933 [1]. Haemophilusinfluenzae is a Gram-ve coccobacillus belonging to the Pasteurellaceae family. It is microscopic in size, ranging from 0.3 to 1 micrometers. Its facultative anaerobic can survive with or without oxygen and has the ability to change its shape. It grows in an environment with increased levels of carbon dioxide. The development of this organismon chocolate agar is facilitated by a medium that containstwo erythrocyte factors:factor X(hematin) and factor V (phosphopyridine nucleotide). These factors are released when red blood cells are lysed [2] . H.influenzae canbe categorised into six separate categories, known as serotypes a, b, c, d, e, and f, based on the presenceof a polysaccharide capsule. These serotypes are identified by their particular reactivity to serum agglutination. H..influenzae typeb is notable due to its polyribosyl. ribitol phosphate capsule, which is responsible for 95% of invasive diseasein children and over 50% of invasivedisease in adults .Less frequentpathogens, the other capsular kinds, are responsible for a smallerproportion of infections. The majority of isolates are non-typeable , indicating the absence of a polysaccharide. capsule and the resultinglack of agglutination with antiserum[3] .The most commonly encountered and prevailing variantis H.. influenzae type b which primarilyaffects youngsters and individuals with weakened immunesystems. Types A, E, and F are also isolated, although less frequently than type B. C and D are hardly identified. All serotypes, especially type b, are frequently responsible for lower respiratory tract infections, such as pneumonia. In addition, they have the potential to induce variousadditional severe illnesses, including meningitis, epiglottitis, cellulitis, septic.arthritis, as well as empyema and bacteremia as diagram (1) [4] . Diagnostic cultures of blood, cerebrospinal fluid (CSF), and other typicallysterile fluids are obligatory under the suitableconditions. Whenever possible,it is advisable to gram-stain specimens obtained for culture. The presence of capsular antigen in blood, CSF, or concentrated urine can be detected using immunoelectrophoresis, latex agglutination, or enzyme-linked immunosorbent assay. This diagnostic method can identifythe antigen in up to 90 percent of cases of meningitis that have been confirmed through culture.Untreated Haemophilus influenzae infection can lead to immediatefatality, especially throughmeningitis and epiglottitis. Currently, there is a tendency to utilize certain injectable third generation cephalosporins as the first treatmentoption for potentially life-threatening Haemophilus influenzae infections in children older than the newborn stage. The typically used drugs for this purpose are cefotaxime or ceftriaxone. Supportive care is crucial in managing Haemophilus influenzaeinfection in children,in addition to antibiotic therapy [5].
Diagram (1) [6]
This diagram shows the how the types of the bacteria can cause infections, in which bacteriadivided to encapsulated and encapsulated. 1- Unencapsulated bacteria are part of normal flora of upper respiratory tract may cause mild infection inchildlike otitis media, conjunctivitis and bronchitis. 2- Encapsulated bacteria mainly type b is the most virulent strain that invades mucosa by IgA protease in the bloodstream that cause systemicdiseases may complicated to bacteremia or encapsulated bacteriaproduce endotoxin that induce inflammation lead to appearance of symptoms of bacterial infection.
The pathogenicity determinants of H. influenzae contribute to its capacity to colonies and induce illness in the host. The following are important virulencefactors of H. influenzae:
1.1 Capsule
The polysaccharide capsuleof H.influenzae is a significant determinant of its abilityto cause disease.The bacterium uses inhibition of phagocytosis to avoid detectionby the host's immune system [7]. H.influenzae serotypes are categorized accordingto their capsularantigens, with the type b (Hib) capsulebeing specifically linked to invasiveillnesses .The capsuleof Haemophilus influenzae is a significant virulence factor due to its antiphagocytic properties, which provide protection against phagocytosis by macrophages or neutrophils. H.influenzae is able to evade destruction and adhere to epithelial cells in the airways[8]. The nativetype B capsule consists of linear teichoicacid, which containsribose, ribitol,and phosphate, and is referredto as such. Polyribosyl-ribitol-phosphate is a compound.The process of capsule synthesis is determined by the capB genes, which exist in two identical copies (17-18 kb) within the chromosome and are connected by a small area (1-1.3kb). The genetic sequencein this area includes a gene known as bexA, which is responsible for producing a protein necessary for transporting the capsular material to the surface of the cell .The remaining 5 serotypes possess the cap gene alone in a single copy. Approximately 2% of H.influenzae type b individualspossess a single copy of the gene. The absence of the other copy results in the inability to produce capsules,and these strainsare referred to as capsule-deficient mutants [9]. Contraryto encapsulated type b bacteria, which are linked to decreased ability to stick to and invade host cells, mutant strainshave a significantly. Enhanced capacityto adhere and infiltrate the macro organism,occurring at a frequency of 50 times [10].
1.2 Pili
Pili are adhesion molecules that enable the binding of cells or microorganisms to surfaces. Pili and non- pilus adhesions aid in the adherence of H.influenzae tohost cells, facilitating colonization and the initiation of infection [11] . The pili are an additionalelement that contributes to the pathogenicity of H.influenzae. They are present in the encapsulated strains of serotype b and in over 50% of the cases. Encapsulated strains.The composition of these structures includes a single substantial protein(HifA) together with two minor proteins (HifD and HifE).Pili facilitate the adherence of the bacterial cell to the eukaryotic cell by attachingto glycoproteins and glycolipids on the eukaryotic cell's surface. H.influenzae possesses a single copyof each gene that encodes fimbria proteins, namely hifA, hifD and hifE. Within this gene cluster, there are two additional genes (hifV and hifS) that encode proteins responsible for synthesizing and protectingfimbria proteins during their export from the cell. Non typable H.influenzae possesses an additional fimbriaprotein known as P5-fibrin, which bears resemblance to one of the outer membrane proteins (P5) [12]. Exterior membrane The number of H.influenzae proteins ranges from six to eight. Some of these antigens, such as P2 and P6, are currentlyundergoing intensive research.May be used into vaccineformulations targeting none capsulated pathogens. Antibodies targeting P2 have bactericidal properties and provide protection. P2 proteins are the predominant outer membrane proteins. These are porins characterized by a very changeable outer portion that exhibits differences among different strains. Their intracellular region,situated within the outer membrane, possesses a conserved amino acid sequence. The extrinsic region of these proteins may undergo temporalvariations due to individual modifications in the structural genes associated with P2. This results in a persistent manifestation of certainH.influenzae infections.P6 is a proteinlocated on the outer membrane that is produced on the surface of both encapsulated and non typablestrains. The gene responsible for encoding it exhibits a significant level of conservation, resulting in a notable similarity in terms of its nucleotide sequence across various strains [13].
1.3 IgA Protease
H.influenzae secretes IgA1 protease, an enzyme that specifically splits human IgA1 antibodies. This enzyme facilitates the evasion of the host's mucosal immune responsesby the bacteria [14]. The IgA1 proteaseis a crucial element in determining the pathogenicity of H.influenzae. It works by deactivating human immunoglobulin A1 and aiding in the colonization of mucosae. Approximately 95%of strains that cannot be typed possess the gene responsible for encoding this enzyme is known asn iga. The protease activity is maintained to a higher degree in invasive isolates blood and cerebrospinal fluid and isolates obtainedfrom sputum. This particular virulence factor is more commonly seen in strainsoriginating from the upper respiratory tract, particularly in non typable strains. A second IgA protease has been identified, which is more prevalent in isolates from individuals with COPD [15].
1.4 Endotoxin (Lipopolysaccharide - LPS):
H.influenzae, similarto other Gram-vebacteria, contains endotoxinon its outer membrane. This endotoxin has the ability to initiate an inflammatoryreaction in the host [16]. H. influenzae, like other Gram-ve microbes, possesses a lipopolysaccharide. However, its lipopolysaccharide has a shorterpolysaccharide chain and is referredto as lipooligosaccharide. Aside from having the distinct lipooligosaccharide, which is a characteristic feature of Gram-vebacteria's endotoxins, aids in evading the process of opsonization and phagocytosis by mimicking molecular structures found in the host organism. This is becausethe lipooligosaccharide has ends that are sialated, meaning they have sialic acid attached to them. These sialated ends have a comparable structureand antigenic properties to the sialatedoligosaccharides found in the sphingolipids of the human body [17].
1.5 Beta- lactamase
Beta-lactamase is a bacterial enzyme that provides resistance to beta-lactam antibiotics, such as penicillins and cephalosporins. H.influenzae has the ability to generate beta-lactamase, which is a method it employs to counteract the impact of beta-lactam antibiotics. The enzyme hydrolyzes the beta-lactam ring compound found in these antibiotics, causingthem to lose their efficacyagainst the bacterium [18] . The phenomenon of ampicillin resistance in H.influenzae was first documented in the early 1970s [19]. β-Lactams have historically been employed for the treatment of H.influenzae infections, but, resistance has arisen and spread. Ampicillin resistance in bacteriaH.influenzae has become prevalent worldwide, with varied incidencerates ranging from 8 to 30% in diverse European countries and North America, to over 50% in certainEastern Asian countries[20]. There have been two described mechanisms of β- lactam resistance. One method involvesthe breakdown of β-lactam by enzymes called (?TEM-1 or ROB-1 β-lactamases. Bacteriawith these enzymesare referred to be β-lactamase-positive ampicillin-resistant. The other involves decreased β-lactam affinityfor penicillin bindingprotein 3 owing to changein the ftsI gene [21].
The classification of H.influenzae that is resistant to antimicrobial agents is intricate. The term often used, β-lactamase-negative ampicillin-resistant is applied to isolates that exhibit resistance to ampicillin, but do not show any indication of β- lactamase [22] . The isolates exhibited resistance to Ampicillin as a result ofsignificant changes in theftsI gene, which encodes the penicillin-binding protein3. These mutationscaused a decreasein the affinity for β-lactam [22]. Nevertheless, certain isolates exhibited such changes, yet were not the strain has demonstrated resistance to ampicillin asdetermined by phenotypic testing. Isolates that have criticalmutations in penicillin-binding protein 3 , regardless of their resistance profile, are classified as genomic BLNAR [23] . The term often used is "β-lactamase positive" in reference to amoxicillin. The term "clavulanic acid-resistant" (BLPACR) refers to isolates that have resistance to amoxicillin/clavulanic acid and show indications of β-lactamase synthesis . The identified isolates were found to have both the β-lactamase gene and significant mutations in the ftsI gene [1]. Certain isolates had this profile, however,they did not demonstrate resistance to amoxicillin clavulanic acid based on phenotypic testing. The genomic BLPACR isolatesare denoted as genomic BLNAR[22]. Resistance caused by modifiedpenicillin- binding proteinshas become a significant mechanismof β-lactam resistance in various bacterialpathogens, including non typeable H.influenzae . In recent years, numerousnations have shown a significant rise in the occurrence of BLNAR non typeable H.influenzae isolates, especially among respiratory tract isolates [23] . Geno typically characterized BLNAR isolates make up 15-30% of all non typeableH.influenzae isolates in Australia the USA and Europe, and a concerning 50% in Japan[24].
1.6 Pathogenesis
The exact mechanismby which H.influenzae infections develop is not fully comprehended, however, the presence of the type b polysaccharide capsulesignificantly contributes to its abilityto cause disease.Enclosed microorganisms have the ability to enter the epithelium of the nasopharynx and directly infiltrate blood vessels. Non typable strainshave reduced invasiveness, although they, alongwith typable strains,elicit an inflammatory response that leads to disease; the significance of exotoxingeneration in pathogenicity is not considered significant. The nasopharynx of the majority of healthy personsis colonized by non- typeableH.influenzae strains, while type b H.influenzae strains are presentin just a small percentage (1 to 2 percent) of normal youngsters. Occurrences of type b infection are prevalent, particularly in nurseries and child care centers. In such cases, the preventive use of antibiotics may be employed. Immunization with type b polysaccharide has shown efficacy in avoiding infection, and vaccines are currently accessible for regular [25].
Figure (1) [26] .
This figure shows some of important virulencefactors that are required for the pathogenesis of H.infleunzae including 1- Polysaccharide capsule which is important for inhibition of phagocytosis to avoid detection by the host's immune system. 2- Are adhesion molecules that enable the binding of cells or microorganisms to surfaces. Pili adhesions aid in the adherence of H.influenzae to host cells, facilitating colonization and the initiation of infection .
Haemophilus influenzae is a pathogenic bacteriumthat frequently leads to seriousinfections, especially in newborns. Haemophilus influenzae is a Gram-vecoccobacillus belonging to the Pasteurellaceae family. It is microscopic in size, ranging from 0.3 to 1 micrometers. Its facultative anaerobic can survive with or without oxygen and has the ability to change its shape. It grows in an environment with increased levels of carbon dioxide. The development of this organismon chocolate agar is facilitated by a medium that contains two erythrocyte factors: factor X (hematin) and factor V (phosphopyridine nucleotide). These factors are released when red blood cells are lysed. H.influenzae can be categorised into six separatecategories, known as serotypes a, b, c, d, e, and f, based on the presence of a polysaccharide capsule. Types A, E, and F are also isolated, although less frequently than type B. C and D are hardly identified. All serotypes, especially type b, are frequently responsible for lower respiratory tract infections, such as pneumonia.In addition, they have the potential to induce variousadditional severe illnesses, including meningitis, epiglottitis, cellulitis, septic.arthritis, as well as empyema and bacteremia. The pathogenicity determinants of H.influenzae contribute to its capacity to colonies and induce illness in the host. The followingare important virulence factors of H.influenzae Capsule The polysaccharide capsuleof H.influenzae is a significant determinant of its abilityto cause disease.The bacterium uses inhibition of phagocytosis to avoid detectionby the host's immune system. Pili : are adhesion molecules that enable the bindingof cells or microorganisms to surfaces. Pili and non-pilusadhesions aid in the adherence of H.influenzae to host cells, facilitating colonization and the initiation of infection. IgA Protease H.influenzae secretes IgA1 protease, an enzymethat specifically splits human IgA1 antibodies. Endotoxin(Lipopolysaccharide - LPS) H.influenzae similar to other Gram- ve bacteria, containsendotoxin on its outer membrane.This endotoxin has the ability to initiate an inflammatory reaction in the host. Beta- lactamaseBeta- lactamase is a bacterialenzyme that providesresistance to beta-lactam antibiotics, such as penicillins and cephalosporins. H.influenzae has the ability to generate beta-lactamase, which is a method it employs to counteract the impact of beta-lactam antibiotics. The enzyme hydrolyzes the beta-lactam ring compound found in these antibiotics, causingthem to lose their efficacyagainst the bacterium.
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.
