1887

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Volume 71, Issue 8

Do plasmids containing heavy metal resistance genes play a role in neonatal sepsis and invasive disease caused by and ? Open Access

Abstract

species are some of those most implicated in neonatal sepsis. However, many isolates from infections appear unremarkable; they are generally susceptible to antibiotics and often of sporadic types not associated with virulence.

Investigation is needed to identify if such isolates have virulence characteristics.

To sequence multiple isolates of a range of types from cases of neonatal invasive disease to identify elements that may explain their virulence, and to determine if such elements are more common among these isolates than generally.

In total, 14 isolates of / belonging to 13 distinct types from blood or CSF from neonatal infections were sequenced using long-read nanopore technology. PCR assays were used to screen a general set of isolates for heavy metal resistance genes , and .

Overall, 12/14 isolates carried one or more plasmids. Ten carried a large plasmid (186 to 310 kb) containing heavy metal resistance genes associated with hypervirulence plasmids, with most (nine) carrying genes for resistance to copper, silver and one other heavy metal (arsenic, tellurite or mercury), but lacking the genes encoding capsule-upregulation and siderophores. Most isolates (9/14) lacked any additional antibiotic resistance genes other than those intrinsic in the species. However, a representative of an outbreak strain carried a plasmid containing , , _IIa, , , ), ), and , but no heavy metal resistance genes. , and were widely found among 100 further isolates screened, with most carbapenemase-gene-positive isolates (20/27) carrying at least one.

Plasmids containing heavy metal resistance genes were a striking feature of isolates from neonatal sepsis but are widely found. They share elements in common with virulence and antibiotic resistance plasmids, perhaps providing a basis from which such plasmids evolve.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): heavy metal resistance plasmids and Klebsiella pneumoniae neonatal sepsis
© 2022 Crown Copyright
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-08-16
2024-05-03
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References

  1. Bandyopadhyay T, Kumar A, Saili A, Randhawa VS. Distribution, antimicrobial resistance and predictors of mortality in neonatal sepsis. J Neonatal Perinatal Med 2018; 11:145–153 [View Article] [PubMed]
     [Google Scholar]
  2. Li X, Ding X, Shi P, Zhu Y, Huang Y et al. Clinical features and antimicrobial susceptibility profiles of culture-proven neonatal sepsis in a tertiary children’s hospital, 2013 to 2017. Medicine (Baltimore) 2019; 98:e14686 [View Article] [PubMed]
     [Google Scholar]
  3. Verma P, Berwal PK, Nagaraj N, Swami S, Jivaji P et al. Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. Int J Contemp Pediatr 2015; 2:176–180 [View Article]
     [Google Scholar]
  4. Russo TA, Marr CM. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev 2019; 32:e00001-19 [View Article] [PubMed]
     [Google Scholar]
  5. Wyres KL, Lam MMC, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 2020; 18:344–359 [View Article] [PubMed]
     [Google Scholar]
  6. Turton JF, Payne Z, Coward A, Hopkins KL, Turton JA et al. Virulence genes in isolates of Klebsiella pneumoniae from the UK during 2016, including among carbapenemase gene-positive hypervirulent K1-ST23 and “non-hypervirulent” types ST147, ST15 and ST383. J Med Microbiol 2018; 67:118–128 [View Article] [PubMed]
     [Google Scholar]
  7. Turton J, Davies F, Turton J, Perry C, Payne Z et al. Hybrid resistance and virulence plasmids in “High-Risk” clones of Klebsiella pneumoniae, including those carrying blaNDM-5. Microorganisms 2019; 7:326 [View Article]
     [Google Scholar]
  8. Li R, Cheng J, Dong H, Li L, Liu W et al. Emergence of a novel conjugative hybrid virulence multidrug-resistant plasmid in extensively drug-resistant Klebsiella pneumoniae ST15. Int J Antimicrob Agents 2020; 55:105952 [View Article] [PubMed]
     [Google Scholar]
  9. Potter RF, Lainhart W, Twentyman J, Wallace MA, Wang B et al. Population structure, antibiotic resistance, and uropathogenicity of Klebsiella variicola. mBio 2018; 9:e02481-18 [View Article] [PubMed]
     [Google Scholar]
  10. Andrade BGN, de Veiga Ramos N, Marin MFA, Fonseca EL, Vicente ACP. The genome of a clinical Klebsiella variicola strain reveals virulence-associated traits and a pl9-like plasmid. FEMS Microbiol Lett 2014; 360:13–16 [View Article] [PubMed]
     [Google Scholar]
  11. Rodríguez-Medina N, Barrios-Camacho H, Duran-Bedolla J, Garza-Ramos U. Klebsiella variicola: an emerging pathogen in humans. Emerg Microbes Infect 2019; 8:973–988 [View Article] [PubMed]
     [Google Scholar]
  12. Farzana R, Jones LS, Rahman MA, Andrey DO, Sands K et al. Outbreak of hypervirulent multidrug-resistant Klebsiella variicola causing high mortality in neonates in Bangladesh. Clin Infect Dis 2019; 68:1225–1227 [View Article] [PubMed]
     [Google Scholar]
  13. Piepenbrock E, Higgins PG, Wille J, Xanthopoulou K, Zweigner J et al. Klebsiella variicola causing nosocomial transmission among neonates - an emerging pathogen?. J Med Microbiol 2020; 69:396–401 [View Article] [PubMed]
     [Google Scholar]
  14. Jajoo M, Manchanda V, Chaurasia S, Sankar MJ, Gautam H et al. Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India. PLoS One 2018; 13:e0180705 [View Article] [PubMed]
     [Google Scholar]
  15. Mohsen L, Ramy N, Saied D, Akmal D, Salama N et al. Emerging antimicrobial resistance in early and late-onset neonatal sepsis. Antimicrob Resist Infect Control 2017; 6:63 [View Article] [PubMed]
     [Google Scholar]
  16. Mukherjee S, Naha S, Bhadury P, Saha B, Dutta M et al. Emergence of OXA-232-producing hypervirulent Klebsiella pneumoniae ST23 causing neonatal sepsis. J Antimicrob Chemother 2020; 75:2004–2006 [View Article] [PubMed]
     [Google Scholar]
  17. Khaertynov KS, Anokhin VA, Rizvanov AA, Davidyuk YN, Semyenova DR et al. Virulence factors and antibiotic resistance of Klebsiella pneumoniae strains isolated from neonates with sepsis. Front Med (Lausanne) 2018; 5:225 [View Article] [PubMed]
     [Google Scholar]
  18. Wang J, Bleich R, Zarmer S, Zhang S, Dogan B et al. Long-read sequencing to interrogate strain-level variation among adherent-invasive Escherichia coli isolated from human intestinal tissue. PLoS One 2021; 16:e0259141 [View Article]
     [Google Scholar]
  19. Li H. Minimap and miniasm: fast mapping and de novo assembly for noisy long sequences. Bioinformatics 2016; 32:2103–2110 [View Article] [PubMed]
     [Google Scholar]
  20. Vaser R, Sović I, Nagarajan N, Šikić M. Fast and accurate de novo genome assembly from long uncorrected reads. Genome Res 2017; 27:737–746 [View Article] [PubMed]
     [Google Scholar]
  21. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article] [PubMed]
     [Google Scholar]
  22. Carattoli A, Zankari E, Garcia-Fernandez A, Voldby Larsen M, Lund O et al. PlasmidFinder and pmlst: in silico detection and typing of plasmids. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article]
     [Google Scholar]
  23. Institut Pasteur Klebsiella Sequence Typing database. n.d https://bigsdb.pasteur.fr/klebsiella/
  24. Petkau A, Stuart-Edwards M, Stothard P, Van Domselaar G. Interactive microbial genome visualization with GView. Bioinformatics 2010; 26:3125–3126 [View Article] [PubMed]
     [Google Scholar]
  25. National Center for Biotechnology Information Basic Local Alignment Search Tool; 2021 https://blast.ncbi.nlm.nih.gov/Blast.cgi
  26. Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res 2006; 34:D32–6 [View Article] [PubMed]
     [Google Scholar]
  27. Tang H-L, Chiang M-K, Liou W-J, Chen Y-T, Peng H-L et al. Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation. Eur J Clin Microbiol Infect Dis 2010; 29:689–698 [View Article] [PubMed]
     [Google Scholar]
  28. Lery LMS, Frangeul L, Tomas A, Passet V, Almeida AS et al. Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor. BMC Biol 2014; 12:41 [View Article] [PubMed]
     [Google Scholar]
  29. Villa L, Poirel L, Nordmann P, Carta C, Carattoli A. Complete sequencing of an IncH plasmid carrying the blaNDM-1, blaCTX-M-15 and qnrB1 genes. J Antimicrob Chemother 2012; 67:1645–1650 [View Article] [PubMed]
     [Google Scholar]
  30. Budde PP, Davis BM, Yuan J, Waldor MK. Characterization of a higBA toxin-antitoxin locus in Vibrio cholerae. J Bacteriol 2007; 189:491–500 [View Article] [PubMed]
     [Google Scholar]
  31. Håkonsholm F, Hetland MAK, Svanevik CS, Sundsfjord A, Lunestad BT et al. Antibiotic sensitivity screening of Klebsiella spp. and Raoultella spp. isolated from marine bivalve molluscs reveal presence of CTX-M-producing K. pneumoniae. Microorganisms 2020; 8:1909 [View Article]
     [Google Scholar]
  32. Passet V, Brisse S. Association of tellurite resistance with hypervirulent clonal groups of Klebsiella pneumoniae. J Clin Microbiol 2015; 53:1380–1382 [View Article]
     [Google Scholar]
  33. Xie M, Chen K, Ye L, Yang X, Xu Q et al. Conjugation of virulence plasmid in clinical Klebsiella pneumoniae strains through formation of a fusion plasmid. Adv Biosyst 2020; 4:e1900239 [View Article]
     [Google Scholar]
  34. Ben Fekih I, Zhang C, Li YP, Zhao Y, Alwathnani HA et al. Distribution of arsenic resistance genes in prokaryotes. Front Microbiol 2018; 9:2473 [View Article]
     [Google Scholar]
  35. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017; 390:1770–1780 [View Article]
     [Google Scholar]
  36. Lu J, Peng Y, Wan S, Frost LS, Raivio T et al. Cooperative function of TraJ and ArcA in regulating the F plasmid tra operon. J Bacteriol 2019; 201:e00448-18 [View Article] [PubMed]
     [Google Scholar]
  37. Lee M, Choi T-J. Species transferability of Klebsiella pneumoniae carbapenemase-2 isolated from a high-risk clone of Escherichia coli ST410. J Microbiol Biotechnol 2020; 30:974–981 [View Article] [PubMed]
     [Google Scholar]
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Do plasmids containing heavy metal resistance genes play a role in neonatal sepsis and invasive disease caused by Klebsiella pneumoniae and Klebsiella variicola?
J. Med. Microbiol. 71, 001486 (2022); https://doi.org/10.1099/jmm.0.001486
/content/journal/jmm/10.1099/jmm.0.001486
/content/journal/jmm/10.1099/jmm.0.001486
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