The virulence factors and pathogenicity of K. pneumoniae isolates are mainly mediated by four major classes of virulence factors that showed in detail in (Figure1-1) include: capsular polysaccharide, lipopolysaccharide (LPS), fimbriae (type l and type3), and siderophores. Capsular polysaccharide (CPS) is an extracellular polysaccharide matrix tightly bound to the bacterial cell wall, which save the bacterium from resists killing by bactericidal serum factors and phagocytosis (Paczosa and Mecsas, 2016). Lipopolysaccharide (LPS) molecule is an external membrane ingredient of the cell, composed of three distinct parts: a core polysaccharide, a side chain called the O-antigen (O-Ag) polysaccharide (Oligosaccharide) and lipid A (phosphate amine glucose fatty acids). O-antigen prevents complement protein deposition and complement associated serum lytic activity (Clements et al., 2008).

Mucosity character of K. pneumoniae isolates protects it from the interaction with anticapsule-specific antibodies to evade phagocytosis (Nelson et al., 2007). In the mid 1980s, hypervirulent K.pneumoniae isolates, mostly connected with the hypermucoviscosity phenotype, has appeared as a clinically considerable pathogen accountable for serious disseminated infections, in a generally healthier population and younger (Lee et al., 2017). Furthermore, adhesion (colonization factors): pili or fimbrial adherence fact or needed for attachment the epithelial cell of the host, such as type 1 and type 3. Siderophores are high-affinity iron assimilation systems that supply iron to the bacterial cells conversely the production of siderophores resulting in emproved growth in the host tissues. Cytotoxins, enterotoxins and haemolysin, heat-stable endotoxins, heat-labile exotoxin and protein tyrosine kinase, are other factors that play a part in pathogenicity of K. pneumoniae (Clegg and Murphy, 2017).

Pili along with capsular polysaccharide and LPS contribute biofilm formation. Isolates in biofilm exhibit innate resistance toward immune responses, antibiotics treatments, and protection from environmental harsh conditions. Biofilm is an important factor contributing to the pathogenesis of K. pneumoniae in causing severe infections. Biofilms not only present a diffusion barrier to oxygen, nutrients, and antibiotics but also the bacterial cells within biofilm have significantly different gene expression patterns as compared to their planktonic bacterial cells. Gene expression can even be different in neighboring cells. This has led to the different physiological states of cells, the cells on the outer surface of a biofilm are growing aerobically and metabolically active. Inside biofilm, a limitation of nutrients causes growing fermentative, dormant (persister or very slow-growing cells) or dead (Crabbé et al., 2019).

References

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1- Clegg, S., & Murphy, C. N. (2017). Epidemiology and virulence of Klebsiella pneumoniae. Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, 435-457.

2- Clements, A., Gaboriaud, F., Duval, J. F., Farn, J. L., Jenney, A. W., Lithgow, T. Wijburg, O.L.C.; Hartland, E.L. & Strugnell, R. A. (2008). The major surface-associated saccharides of Klebsiella pneumoniae contribute to host cell association. PLoS One, 3(11):1-10.

3- Crabbé, A., Jensen, P. Ø., Bjarnsholt, T., & Coenye, T. (2019). Antimicrobial tolerance and metabolic adaptations in microbial biofilms.

4- Lee, J. S., Choi, J. Y., Chung, E. S., Peck, K. R., & Ko, K. S. (2019). Variation in the formation of persister cells against meropenem in Klebsiella pneumoniae bacteremia and analysis of its clinical features. Diagnostic microbiology and infectious disease, 95(3), 114853.

5- Nelson, A. L., Roche, A. M., Gould, J. M., Chim, K., Ratner, A. J., & Weiser, J. N. (2007). Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance. Infection and immunity, 75(1), 83-90.

6- Paczosa, M. K., & Mecsas, J. (2016). Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol. Mol. Biol. Rev., 80(3), 629-661.