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Antimicrobial resistance dissemination driven by Klebsiella pneumoniae: the role of high-risk clones and high-risk plasmids

Number of pages73
Defense date2023-12-01
Abstract

Background. Carbapenem-resistant ESKAPE pathogen K. pneumoniae plays a critical role driving antimicrobial resistance dissemination. This is mainly mediated by two general fluxes, clonal spread of specific K. pneumoniae high-risk genetic lineages, and horizontal gene transfer through mobile genetic elements such as plasmids. Specific clones, such as ST258 and ST15, have successfully established themselves worldwide; others, as ST307 or ST16 are emerging. Among plasmids some backbones are closely linked to specific carbapenemase dissemination (such as IncFIB-pQIL-KPC and IncL-OXA-48), while other are ubiquitous. Another growing concern is plasmid-mediated hypervirulence, originally associated to distinct clones, converging into the same lineages as carbapenem resistance and vice-versa. Finally, when these lineages acquire last resort colistin or aminoglycoside resistance, it further complicates the epidemiological scenario and clinical management.

Results and Scientific publications. Five publications are presented here. Four are based on a retrospective cohort of 165 patients suffering bloodstream infections due to KPC-producing K. pneumoniae in a tertiary hospital in Latin America. The clinical and molecular description, using bacterial whole-genome sequencing (WGS), is provided. It showed a polyclonal distribution mainly driven by Clonal Complex 258 (ST258, ST11, ST437), the emergence of a ST16 lineage associated to high 30-day crude mortality, and minority cases provoked by other clones including ST15 and ST307. The scientific publications shown here further dissect the molecular features of carbapenemase-bearing plasmids including a unusual IncQ1 plasmid, horizontal spread of a 16SrRNA methylase, as well as chromosomally mediated colistin resistance in K. pneumoniae (sensu stricto) and K. pneumoniae complex subspecies K. variicola.

Discussion. These studies allowed to highlight the importance of the epidemic clone ST258 and its association with aminoglycoside and colistin resistance, and showed how horizontally-acquired and chromosomally vertically-encoded mechanisms co-exist. These publications also identify and describe an emergent ST16 lineage, associated with increased mortality; ST16 was subsequently described in the context of fatal outbreaks in Asia. These studies underscore how instrumental WGS has become to monitor these clonal dissemination patterns, and long-read sequencing technologies, thanks to recent advances, can now address the issue of plasmid transmission and their role in chains of transmission in healthcare settings. Plasmid monitoring is poised to become an important parameter to guide Infection Prevention and Control (IPC) practices.

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Keywords
  • Plasmid
  • Klebsiella pneumoniae
  • ST258
  • ST16
  • ST11
  • Clones
  • Molecular epidemiology
  • Whole genome sequencing
  • AMR
  • WGS
  • Gram-negative
Citation (ISO format)
ANDREY, Diego Olivier. Antimicrobial resistance dissemination driven by <i>Klebsiella pneumoniae</i>: the role of high-risk clones and high-risk plasmids. 2023. doi: 10.13097/archive-ouverte/unige:174101
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