Isolation of new Klebsiella pneumoniae phage PSKP16
Background and Objectives: Klebsiella pneumoniae is a clinically relevant opportunistic pathogen belonging to the Enterobacteriaceae family. It is in the top three bacteria associated with antimicrobial resistance deaths globally, and one of the most dangerous bacteria causing nosocomial infections. Phage therapy offers a potential option for the treatment of drug-resistant bacterial infections.
Materials and Methods: Phage PSKP16 was isolated against K. pneumoniae, capsular type K2 (isolated from a wound infection). PSKP16 is a new lytic phage with a Siphovirus-like morphology.
Results: PSKP16 is a linear double stranded DNA phage with a GC content of 50% and genome size of 46,712 bp, for which we predicted 67 ORFs. PSKP16 belongs to the genus Webervirus and shows high evolutionary proximity to Klebsiella phages JY917, Sushi, and B1.
Conclusion: Phage isolation is fast, cheap and efficient, but it requires time and characterization (which adds expense) to ensure that the isolated phages do not pose a health risk, which is essential to safely use phage therapy to treat life-threatening bacterial infections.
2. Caneiras C, Lito L, Melo-Cristino J, Duarte A. Community-and hospital-acquired Klebsiella pneumoniae urinary tract infections in portugal: virulence and antibiotic resistance. Microorganisms 2019; 7: 138.
3. Shankar C, Nabarro LE, Anandan S, Ravi R, Babu P, Munusamy E, et al. Extremely high mortality rates in patients with carbapenem-resistant, Hypermucoviscous Klebsiella pneumoniae blood stream infections. J Assoc Physicians India 2018; 66: 13-16.
4. Van Laar TA, Chen T, You T, Leung KP. Sublethal concentrations of carbapenems alter cell morphology and genomic expression of Klebsiella pneumoniae biofilms. Antimicrob Agents Chemother 2015; 59: 1707-1717.
5. Vuotto C, Longo F, Pascolini C, Donelli G, Balice MP, Libori MF, et al. Biofilm formation and antibiotic resistance in Klebsiella pneumoniae urinary strains. J Appl Microbiol 2017; 123: 1003-1018.
6. Mollers M, Lutgens SP, Schoffelen AF, Schneeberger PM, Suijkerbuijk AWM. Cost of nosocomial outbreak caused by NDM-1-containing Klebsiella pneumoniae in the Netherlands, October 2015-January 2016. Emerg Infect Dis 2017; 23: 1574-1576.
7. Choby JE, Howard-Anderson J, Weiss DS. Hypervirulent Klebsiella pneumoniae–clinical and molecular perspectives. J Intern Med 2020; 287: 283-300.
8. Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017; 41: 252-275.
9. Sanchez GV, Master RN, Clark RB, Fyyaz M, Duvvuri P, Ekta G, et al. Klebsiella pneumoniae antimicrobial drug resistance, United States, 1998–2010. Emerg Infect Dis 2013; 19: 133-136.
10. Herridge WP, Shibu P, O’Shea J, Brook TC, Hoyles L. Bacteriophages of Klebsiella spp., their diversity and potential therapeutic uses. J Med Microbiol 2020; 69: 176-194.
11. Hung C-H, Kuo C-F, Wang C-H, Wu C-M, Tsao N. Experimental phage therapy in treating Klebsiella pneumoniae-mediated liver abscesses and bacteremia in mice. Antimicrob Agents Chemother 2011; 55: 1358-1365.
12. Townsend EM, Kelly L, Gannon L, Muscatt G, Dunstan R, Michniewski S, et al. Isolation and characterization of Klebsiella phages for phage therapy. Phage (New Rochelle) 2021; 2: 26-42.
13. Keen EC. Phage therapy: concept to cure. Front Microbiol 2012; 3: 238.
14. Kortright KE, Chan BK, Koff JL, Turner PE. Phage therapy: a renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe 2019; 25: 219-232.
15. El Haddad L, Harb CP, Gebara MA, Stibich MA, Chemaly RF. A systematic and critical review of bacteriophage therapy against multidrug-resistant ESKAPE organisms in humans. Clin Infect Dis 2019; 69: 167-178.
16. Ly-Chatain MH. The factors affecting effectiveness of treatment in phages therapy. Front Microbiol 2014; 5: 51.
17. Monteiro R, Pires DP, Costa AR, Azeredo J. Phage therapy: going temperate? Trends Microbiol 2019; 27: 368-378.
18. Brussow H, Canchaya C, Hardt W-D. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol Mol Biol Rev 2004; 68: 560-602.
19. Feizabadi MM, Raji N, Delfani S. Identification of Klebsiella pneumoniae K1 and K2 Capsular types by PCR and quellung test. Jundishapur J Microbiol 2013; 6(9): e7585.
20. Terzian P, Olo Ndela E, Galiez C, Lossouarn J, Pérez Bucio RE, Mom R, et al. PHROG: families of prokaryotic virus proteins clustered using remote homology. NAR Genom Bioinform 2021; 3: Iqab067.
21. Cook R, Brown N, Redgwell T, Rihtman B, Barnes M, Clokie M, et al. INfrastructure for a PHAge reference database: identification of large-scale biases in the current collection of cultured phage genomes. Phage (New Rochelle) 2021; 2: 214-23.
22. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 2018; 35: 1547-1549.
23. Majkowska-Skrobek G, Łątka A, Berisio R, Maciejewska B, Squeglia F, Romano M, et al. Capsule-targeting depolymerase, derived from Klebsiella KP36 phage, as a tool for the development of anti-virulent strategy. Viruses 2016; 8: 324.
24. Latka A, Leiman PG, Drulis-Kawa Z, Briers Y. Modelling the architecture of depolymerase-containing receptor binding proteins in Klebsiella phages. Front Microbiol 2019; 10: 2649.
25. Wang C, Li P, Niu W, Yuan X, Liu H, Huang Y, et al. Protective and therapeutic application of the depolymerase derived from a novel KN1 genotype of Klebsiella pneumoniae bacteriophage in mice. Res Microbiol 2019; 170: 156-164.
26. Palmieri M, Wyres KL, Mirande C, Qiang Z, Liyan Y, Gang C, et al. Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones. Microb Genom 2019; 7: 000520.
27. Lin C-L, Chen F-H, Huang L-Y, Chang J-C, Chen J-H, Tsai Y-K, et al. Effect in virulence of switching conserved homologous capsular polysaccharide genes from Klebsiella pneumoniae serotype K1 into K20. Virulence 2017; 8: 487-493.
28. Lee IR, Molton JS, Wyres KL, Gorrie C, Wong J, Hoh CH, et al. Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci Rep 2016; 6: 29316.
29. Pan Y-J, Lin T-L, Chen Y-Y, Lai P-H, Tsai Y-T, Hsu C-R, et al. Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types. Microb Biotechnol 2019; 12: 472-486.
30. Solovieva EV, Myakinina VP, Kislichkina AA, Krasilnikova VM, Verevkin VV, Mochalov VV, et al. Comparative genome analysis of novel Podoviruses lytic for hypermucoviscous Klebsiella pneumoniae of K1, K2, and K57 capsular types. Virus Res 2018; 243: 10-18.
31. Knecht LE, Veljkovic M, Fieseler L. Diversity and function of phage encoded depolymerases. Front Microbiol 2020; 10: 2949.
32. Lin T-L, Hsieh P-F, Huang Y-T, Lee W-C, Tsai Y-T, Su P-A, et al. Isolation of a bacteriophage and its depolymerase specific for K1 capsule of Klebsiella pneumoniae: implication in typing and treatment. J Infect Dis 2014; 210: 1734-1744.
|Issue||Vol 15 No 1 (2023)|
|Klebsiella pneumoniae; Bacteriophages; Drug resistance; Infection control; High throughput nucleotide sequencing|
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|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|