Genomic insights into the diversity, virulence and resistance of extensively drug resistant clinical isolates Open Access

Abstract

has been implicated in wide-ranging nosocomial outbreaks, causing severe infections without effective treatments due to antibiotic resistance. Here, we performed genome sequencing of 70 extensively drug resistant clinical isolates, collected from Brasília’s hospitals (Brazil) between 2010 and 2014. The majority of strains (60 out of 70) belonged to a single clonal complex (CC), CC258, which has become distributed worldwide in the last two decades. Of these CC258 strains, 44 strains were classified as sequence type 11 (ST11) and fell into two distinct clades, but no ST258 strains were found. These 70 strains had a pan-genome size of 10 366 genes, with a core-genome size of ~4476 genes found in 95 % of isolates. Analysis of sequences revealed diverse mechanisms of resistance, including production of multidrug efflux pumps, enzymes with the same target function but with reduced or no affinity to the drug, and proteins that protected the drug target or inactivated the drug. β-Lactamase production provided the most notable mechanism associated with . Each strain presented two or three different β-lactamase enzymes, including class A (SHV, CTX-M and KPC), class B and class C AmpC enzymes, although no class D β-lactamase was identified. Strains carrying the NDM enzyme involved three different ST types, suggesting that there was no common genetic origin.

Funding
This study was supported by the:
  • Wellcome Trust
    • Principle Award Recipient: DerekJ. Pickard
  • Killam Trusts
    • Principle Award Recipient: RobertE.W. Hancock
  • Michael Smith Foundation for Health Research
    • Principle Award Recipient: RobertE.W. Hancock
  • Fundação de Apoio à Pesquisa do Distrito Federal
    • Principle Award Recipient: OctavioL. Franco
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
    • Principle Award Recipient: OctavioL. Franco
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
    • Principle Award Recipient: OctavioL. Franco
  • Simon Fraser University (Award New Faculty Start-Up Grant)
    • Principle Award Recipient: AmyLee
  • Canadian Institutes of Health Research (Award FDN-154287)
    • Principle Award Recipient: RobertE.W. Hancock
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2021-08-23
2024-03-28
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