Evaluating the Role of Capsular Polysaccharide K and Lipopolysaccharide O antigens in the pathogenesis of Klebsiella pneumoniae Using a Rat Model of Pneumonia

Main Article Content

Hastyar Najmadeen
Fayez Alghofaili

Keywords

Klebsiella pneumoniae, Capsular polysaccharide, Lipopolysacharide O side chain, pneumonia, K-antigens, O-antigens

Abstract

Klebsiella pneumoniae is one of the commonest bacterial causes of hospital acquired pneumonia and accounts for 5 to 7.5% of all nosocomial infections in intensive care units, lower respiratory, urinary tract, and burn wound infections. The objectives of this study are to compare total polysaccharide concentrations extracted from K. pneumoniae isolates. Secondly, to investigate the cellular events using rat model of infection leading to pneumonia with the highest capsular polysaccharide contents as well as evaluating the contributions of each capsular polysaccharide K & lipopolysaccharide O-antigens in this process. For this purpose, thirty-nine strains of K. pneumoniae were isolated from nosocomial infections at Sulaimaniyha hospitals. Capsular polysaccharides and total polysaccharide in all isolated K. pneumoniae strains, were extracted by heating method and quantification were determined on the bases of standard glucose curve. Results revealed that K. pneumoniae was significantly different in their capsular polysaccharide concentrations with regard to their site of isolation. The highest polysaccharide content was found in a clinical isolate of blood specimens (80μg / 1010 CFU/ ml). Histopathological examinations were performed on rats suffering from induced pneumonia with whole bacterial cell antigens, extracted capsular polysaccharide (K-antigens), and (O-antigens). In the case of whole bacterial cells, lung sections showed severe effects; the outpouring of polymorphonuclear and mononuclear leukocytes to the interalveolar septa, accompanied by destruction of alveolar walls (emphysema) with severe congestion of blood vessels, peribronchiolar and perivascular infiltration of inflammatory cells. K-antigens exhibited relatively whole bacterial cells-like histopathological effects whereas O-antigens did not reveal such profound effects.

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References

1. Neu HC. The crisis in antibiotic resistance. Science. 1992;257(5073):1064-73.
2. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev. 1998;11(4):589-603.
3. Meatherall BL, Gregson D, Ross T, Pitout JD, Laupland KB. Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia. The American journal of medicine. 2009;122(9):866-73.
4. Folgori L, Bernaschi P, Piga S, Carletti M, Cunha FP, Lara PHR, et al. Healthcare-associated infections in pediatric and neonatal intensive care units: impact of underlying risk factors and antimicrobial resistance on 30-day case-fatality in Italy and Brazil. infection control & hospital epidemiology. 2016;37(11):1302-9.
5. Lee C-R, Lee JH, Park KS, Jeon JH, Kim YB, Cha C-J, et al. Antimicrobial resistance of hypervirulent Klebsiella pneumoniae: epidemiology, hypervirulence-associated determinants, and resistance mechanisms.
Frontiers in cellular and infection microbiology. 2017;7:483.
6. Cerceo E, Deitelzweig SB, Sherman BM, Amin AN. Multidrug-resistant gram-negative bacterial infections in the hospital setting: overview, implications for clinical practice, and emerging treatment options. Microbial Drug Resistance. 2016;22(5):412-31.
7. Hegerle N, Choi M, Sinclair J, Amin MN, Ollivault-Shiflett M, Curtis B, et al. Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa. Plos One. 2018;13(9):e0203143.
8. Williams P, Tomas J. The pathogenicity of Klebsiella pneumoniae. Rev Med Microbiol. 1990;1:196-204.
9. Sahly H, Podschun R, Oelschlaeger TA, Greiwe M, Parolis H, Hasty D, et al. Capsule impedes adhesion to and invasion of epithelial cells by Klebsiella pneumoniae. Infection and immunity. 2000;68(12):6744-9.
10. Simoons-Smit A, Verweij-van Vught A, MacLaren D. The role of K antigens as virulence factors in Klebsiella. Journal of medical microbiology. 1986;21(2):133-7.
11. Shankar-Sinha S, Valencia GA, Janes BK, Rosenberg JK, Whitfield C, Bender RA, et al. The Klebsiella pneumoniae O antigen contributes to bacteremia and lethality during murine pneumonia. Infection and immunity. 2004;72(3):1423-30.
12. Follador R, Heinz E, Wyres KL, Ellington MJ, Kowarik M, Holt KE, et al. The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial genomics. 2016;2(8).
13. Clarke BR, Ovchinnikova OG, Kelly SD, Williamson ML, Butler JE, Liu B, et al. Molecular basis for the structural diversity in serogroup O2-antigen polysaccharides in Klebsiella pneumoniae. Journal of Biological Chemistry. 2018;293(13):4666-79.
14. Roberts I, Saunders F, Boulnois G. Bacterial capsules and interactions with complement and phagocytes. Portland Press Ltd.; 1989.
15. Cortés G, Borrell N, de Astorza B, Gómez C, Sauleda J, Albertí S. Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia. Infection and immunity. 2002;70(5):2583-90.
16. Levinson W, Chin-Hong P, Joyce EA, Nussbaum J, Schwartz BS. Review of medical microbiology & immunology : a guide to clinical infectious diseases. Sixteenth edition. ed. New York: McGraw-Hill Education; 2020. xi, 846 pages p.
17. Cryz Jr S, Fürer F, Germanier R. Experimental Klebsiella pneumoniae burn wound sepsis: role of
capsular polysaccharide. Infection and immunity. 1984;43(1):440-1.
18. Domenico P, Schwartz S, Cunha BA. Reduction of capsular polysaccharide production in Klebsiella pneumoniae by sodium salicylate. Infect Immun. 1989;57(12):3778-82.
19. Amako K, Meno Y, Takade A. Fine structures of the capsules of Klebsiella pneumoniae and Escherichia coli K1. Journal of bacteriology. 1988;170(10):4960-2.
20. Merino S, Camprubi S, Alberti S, Benedi V-J, Tomas JM. Mechanisms of Klebsiella pneumoniae resistance to complement-mediated killing. Infection and immunity. 1992;60(6):2529-35.
21. Lai Y-C, Peng H-L, Chang H-Y. RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level. Journal of bacteriology. 2003;185(3):788-800.
22. Nassif X, Fournier JM, Arondel J, Sansonetti PJ. Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect Immun. 1989;57(2):546-52.
23. Ganz T. Antimicrobial polypeptides in host defense of the respiratory tract. The Journal of clinical investigation. 2002;109(6):693-7.
24. Tortora GJ, Funke BR, Case CL, Weber D, Bair III WB. Microbiology: An Introduction, eBook: Pearson Higher Ed; 2020.
25. Athamna A, Ofek I, Keisari Y, Markowitz S, Dutton G, Sharon N. Lectinophagocytosis of encapsulated Klebsiella pneumoniae mediated by surface lectins of guinea pig alveolar macrophages and human monocyte-derived macrophages. Infection and immunity. 1991;59(5):1673-82.
26. Ofek I, Kabha K, Athamna A, Frankel G, Wozniak D, Hasty D, et al. Genetic exchange of determinants for capsular polysaccharide biosynthesis between Klebsiella pneumoniae strains expressing serotypes K2 and K21a. Infection and immunity. 1993;61(10):4208-16.
27. Kabha K, Nissimov L, Athamna A, Keisari Y, Parolis H, Parolis L, et al. Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae. Infection and immunity. 1995;63(3):847-52.
28. Anderson WAD. Pathology1971. 907-8 p.
29. Moorthy AN, Rai P, Jiao H, Wang S, Tan KB, Qin L, et al. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia. Oncotarget. 2016;7(15):19327.
30. Tamaoki J, Sakai N, Isono K, Kanemura T, Takeyama K, Takizawa T. Lipopolysaccharide from Klebsiella pneumoniae inhibits Na+ absorption in canine tracheal epithelium. Infection and immunity. 1991;59(2):716-7.