1887

Abstract

(Kp) has emerged as a global life-threatening pathogen owing to its multidrug resistance and hypervirulence phenotype. Several fatal outbreaks of carbapenem-resistant hypervirulent Kp have been reported recently. Hypermucoviscosity (HMV) is a phenotype commonly associated with hypervirulence of Kp, which is usually regulated by or (regulators of the mucoid phenotype). Here, we found that temperature was important in the HMV phenotype of Kp, and the impact of temperature on HMV was not uniform among strains. We investigated the HMV phenotype at 37 °C and room temperature (20–25 °C) in 170 clinically isolated hypermucoviscous Kp strains in Japan and analysed the association between the HMV phenotype, virulence genes and antimicrobial resistance (AMR) genes. String length distribution at different temperatures was correlated with the genomic population of Kp. The strains carrying / frequently showed the HMV phenotype at 37 °C, while the strains negative for these genes tended to show the HMV phenotype at room temperature. Hypervirulent Kp clusters carrying / without extended-spectrum beta-lactamases (ESBL)/carbapenemases produced higher string lengths at 37 °C than at room temperature, and were mostly isolated from the respiratory tract. Other HMV strains showed distinct characteristics of not carrying / but were positive for ESBL/carbapenemases, with a higher string length at room temperature than at 37 °C, and were frequently isolated from bloodstream infections. In total, 21 (13.5 %) HMV isolates carried ESBL and carbapenemases, among which five isolates were carbapenem-resistant hypervirulent Kp with a pLVPK-like plasmid (an epidemic virulence plasmid) and a pKPI-6-like plasmid (an epidemic -bearing plasmid in Japan), suggesting the convergence of worldwide hypervirulence and epidemic AMR in Japan.

Funding
This study was supported by the:
  • Japan Society for the Promotion of Science (Award JP18K07112)
    • Principle Award Recipient: ShizuoKayama
  • Japan Society for the Promotion of Science (Award JP21K16947)
    • Principle Award Recipient: MiNguyen-Tra Le
  • Japan Agency for Medical Research and Development (Award 21fk0108604j0001)
    • Principle Award Recipient: MotoyukiSugai
  • Japan Agency for Medical Research and Development (Award 20fk0108132j0001)
    • Principle Award Recipient: MotoyukiSugai
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000827
2022-05-27
2024-10-11
Loading full text...

Full text loading...

/deliver/fulltext/mgen/8/5/mgen000827.html?itemId=/content/journal/mgen/10.1099/mgen.0.000827&mimeType=html&fmt=ahah

References

  1. Holt KE, Wertheim H, Zadoks RN, Baker S, Whitehouse CA et al. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proc Natl Acad Sci U S A 2015; 112:E3574–81 [View Article] [PubMed]
    [Google Scholar]
  2. Gu D, Dong N, Zheng Z, Lin D, Huang M et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in A Chinese hospital: A molecular epidemiological study. Lancet Infect Dis 2018; 18:37–46 [View Article] [PubMed]
    [Google Scholar]
  3. Wyres KL, Nguyen TNT, Lam MMC, Judd LM, van Vinh Chau N et al. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia. Genome Med 2020; 12:11 [View Article] [PubMed]
    [Google Scholar]
  4. Wyres KL, Lam MMC, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 2020; 18:344–359 [View Article] [PubMed]
    [Google Scholar]
  5. Shigemoto N, Kuwahara R, Kayama S, Shimizu W, Onodera M et al. Emergence in Japan of an imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae carrying blaIMP-6. Diagn Microbiol Infect Dis 2012; 72:109–112 [View Article] [PubMed]
    [Google Scholar]
  6. Russo TA, Marr CM. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev 2019; 32: [View Article]
    [Google Scholar]
  7. Shon AS, Bajwa RPS, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: A new and dangerous breed. Virulence 2013; 4:107–118 [View Article]
    [Google Scholar]
  8. Kawai T. Hypermucoviscosity: an extremely sticky phenotype of Klebsiella pneumoniae associated with emerging destructive tissue abscess syndrome. Clin Infect Dis 2006; 42:1359–1361 [View Article]
    [Google Scholar]
  9. Catalán-Nájera JC, Garza-Ramos U, Barrios-Camacho H. Hypervirulence and hypermucoviscosity: Two different but complementary Klebsiella spp. phenotypes?. Virulence 2017; 8:1111–1123 [View Article]
    [Google Scholar]
  10. Fang CT, Chuang YP, Shun CT, Chang SC, Wang JT. A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 2004; 199:697–705 [View Article]
    [Google Scholar]
  11. Chuang Y-P, Fang C-T, Lai S-Y, Chang S-C, Wang J-T. Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis 2006; 193:645–654 [View Article]
    [Google Scholar]
  12. Liu YM, Li BB, Zhang YY, Zhang W, Shen H et al. Clinical and molecular characteristics of emerging hypervirulent Klebsiella pneumoniae bloodstream infections in mainland China. Antimicrob Agents Chemother 2014; 58:5379–5385 [View Article]
    [Google Scholar]
  13. Srinivasan VB, Venkataramaiah M, Mondal A, Vaidyanathan V, Govil T et al. Functional characterization of a novel outer membrane porin KpnO, regulated by PhoBR two-component system in Klebsiella pneumoniae NTUH-K2044. PLoS One 2012; 7:e41505 [View Article] [PubMed]
    [Google Scholar]
  14. Walker KA, Miner TA, Palacios M, Trzilova D, Frederick DR et al. A Klebsiella pneumoniae regulatory mutant has reduced capsule expression but retains hypermucoviscosity. mBio 2019; 10:1–16 [View Article]
    [Google Scholar]
  15. Nassif X, Honoré N, Vasselon T, Cole ST, Sansonetti PJ. Positive control of colanic acid synthesis in Escherichia coli by rmpA and rmpB, two virulence-plasmid genes of Klebsiella pneumoniae. Mol Microbiol 1989; 3:1349–1359 [View Article]
    [Google Scholar]
  16. Yu WL, Ko WC, Cheng KC, Lee HC, Ke DS et al. Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin Infect Dis 2006; 42:1351–1358 [View Article] [PubMed]
    [Google Scholar]
  17. Russo TA, Olson R, Fang CT, Stoesser N, Miller M et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J Clin Microbiol 2018; 56:e00776-18 [View Article] [PubMed]
    [Google Scholar]
  18. Wacharotayankun R, Arakawa Y, Ohta M, Tanaka K, Akashi T et al. Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ. Infect Immun 1993; 61:3164–3174 [View Article] [PubMed]
    [Google Scholar]
  19. Walker KA, Miller VL. The intersection of capsule gene expression, hypermucoviscosity and hypervirulence in Klebsiella pneumoniae. Curr Opin Microbiol 2020; 54:95–102 [View Article] [PubMed]
    [Google Scholar]
  20. Alcántar-Curiel MD, Girón JA. Klebsiella pneumoniae and the pyogenic liver abscess: implications and association of the presence of rpmA genes and expression of hypermucoviscosity. Virulence 2015; 6:407–409 [View Article] [PubMed]
    [Google Scholar]
  21. Clinical and Laboratory Standards Institute (CLSI) M100Ed30 | Performance Standards for Antimicrobial Susceptibility Testing 2018
    [Google Scholar]
  22. Lam MMC, Wick RR, Watts SC, Cerdeira LT, Wyres KL et al. A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex. Nat Commun 2021; 12:1–16 [View Article] [PubMed]
    [Google Scholar]
  23. Wyres KL, Wick RR, Gorrie C, Jenney A, Follador R et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb Genom 2016; 2:e000102 [View Article] [PubMed]
    [Google Scholar]
  24. Kaas RS, Leekitcharoenphon P, Aarestrup FM, Lund O. Solving the problem of comparing whole bacterial genomes across different sequencing platforms. PLoS ONE 2014; 9:e104984 [View Article] [PubMed]
    [Google Scholar]
  25. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021; 49:W293–W296 [View Article] [PubMed]
    [Google Scholar]
  26. Pommier T, Canbäck B, Lundberg P, Hagström A, Tunlid A. RAMI: A tool for identification and characterization of phylogenetic clusters in microbial communities. Bioinformatics 2009; 25:736–742 [View Article] [PubMed]
    [Google Scholar]
  27. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLOS Comput Biol 2017; 13:e1005595 [View Article] [PubMed]
    [Google Scholar]
  28. Alikhan N-F, Petty NK, Ben Zakour NL, Beatson SA. BLAST Ring Image Generator (BRIG): simple prokaryote genome comparisons. BMC Genomics 2011; 12:1–10 [View Article] [PubMed]
    [Google Scholar]
  29. Kayama S, Shigemoto N, Kuwahara R, Oshima K, Hirakawa H et al. Complete nucleotide sequence of the IncN plasmid encoding IMP-6 and CTX-M-2 from emerging carbapenem-resistant Enterobacteriaceae in Japan. Antimicrob Agents Chemother 2015; 59:1356–1359 [View Article] [PubMed]
    [Google Scholar]
  30. Feng Y, Lu Y, Yao Z, Zong Z. Carbapenem-resistant hypervirulent Klebsiella pneumoniae of sequence type 36. Antimicrob Agents Chemother 2018; 62:e02644-17 [View Article] [PubMed]
    [Google Scholar]
  31. Shi L, Feng J, Zhan Z, Zhao Y, Zhou H et al. Comparative analysis of blakpc-2-and rmtb-carrying incfii-family pkpc-LK30/phn7a8 hybrid plasmids from Klebsiella pneumoniae CG258 strains disseminated among multiple chinese hospitals. Infect Drug Resist 2018; 11:1783–1793 [View Article]
    [Google Scholar]
  32. Siu LK, Fung C-P, Chang F-Y, Lee N, Yeh K-M et al. Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan. J Clin Microbiol 2011; 49:3761–3765 [View Article] [PubMed]
    [Google Scholar]
  33. Moradigaravand D, Martin V, Peacock SJ, Parkhill J. Evolution and epidemiology of multidrug-resistant Klebsiella pneumoniae in the United Kingdom and Ireland. mBio 2017; 8:e01976-16 [View Article] [PubMed]
    [Google Scholar]
  34. Harada S, Aoki K, Yamamoto S, Ishii Y, Sekiya N et al. Clinical and molecular characteristics of Klebsiella pneumoniae isolates causing bloodstream infections in Japan: occurrence of hypervirulent infections in health care. J Clin Microbiol 2019; 57:e01206-19 [View Article] [PubMed]
    [Google Scholar]
  35. Siu LK, Yeh KM, Lin JC, Fung CP, Chang FY. Klebsiella pneumoniae liver abscess: A new invasive syndrome. Lancet Infect Dis 2012; 12:881–887 [View Article] [PubMed]
    [Google Scholar]
  36. Cheng HY, Chen YS, Wu CY, Chang HY, Lai YC et al. RmpA regulation of capsular polysaccharide biosynthesis in Klebsiella pneumoniae CG43. J Bacteriol 2010; 192:3144–3158 [View Article] [PubMed]
    [Google Scholar]
  37. Yang X, Dong N, Chan EWC, Zhang R, Chen S. Carbapenem resistance-encoding and virulence-encoding conjugative plasmids in Klebsiella pneumoniae. Trends Microbiol 2021; 29:65–83 [View Article] [PubMed]
    [Google Scholar]
  38. Harada S, Aoki K, Ishii Y, Ohno Y, Nakamura A et al. Emergence of IMP-producing hypervirulent Klebsiella pneumoniae carrying a pLVPK-like virulence plasmid. Int J Antimicrob Agents 2019; 53:873–875 [View Article] [PubMed]
    [Google Scholar]
  39. Lee C-R, Lee JH, Park KS, Jeon JH, Kim YB et al. Antimicrobial resistance of hypervirulent Klebsiella pneumoniae: epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front Cell Infect Microbiol 2017; 7:11 [View Article] [PubMed]
    [Google Scholar]
/content/journal/mgen/10.1099/mgen.0.000827
Loading
/content/journal/mgen/10.1099/mgen.0.000827
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error