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Clinical Infectious Diseases A 4.5-Year Within-Patient Evolution of a Colistin-Resistant Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Sequence Type 258

Abstract : Background. Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) has emerged globally over the last decade as a major nosocomial pathogen that threatens patient care. These highly resistant bacteria are mostly associated with a single Kp clonal group, CG258, but the reasons for its host and hospital adaptation remain largely unknown. Methods. We analyzed the in vivo evolution of a colistin-resistant KPC-Kp CG258 strain that contaminated a patient following an endoscopy and was responsible for a fatal bacteremia 4.5 years later. Whole-genome sequencing was performed on 17 KPC-Kp isolates from this patient; single-nucleotide polymorphisms were analyzed and their implication in antimicrobial resistance and bacterial host adaptation investigated. Results. The patient KPC-Kp strain diversified over 4.5 years at a rate of 7.5 substitutions per genome per year, resulting in broad phenotypic modifications. After 2 years of carriage, all isolates restored susceptibility to colistin. Higher expression of the fimbriae conferred the ability to produce more biofilm, and the isolate responsible for a bacteremia grew in human serum. The convergent mutations occurring in specific pathways, such as the respiratory chain and the cell envelope, revealed a complex long-term adaptation of KPC-Kp. Conclusions. Broad genomic and phenotypic diversification and the parallel selection of pathoadaptive mutations might contribute to long-term carriage and virulence of KPC-Kp CG258 strains and to the dissemination of this clone.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02565607
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Submitted on : Wednesday, May 6, 2020 - 3:43:22 PM
Last modification on : Wednesday, October 14, 2020 - 1:00:06 PM

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Agnès Jousset, Rémy Bonnin, Isabelle Rosinski-Chupin, Delphine Girlich, Gaelle Cuzon, et al.. Clinical Infectious Diseases A 4.5-Year Within-Patient Evolution of a Colistin-Resistant Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Sequence Type 258. Clinical Infectious Diseases, Oxford University Press (OUP), 2018, 67 (9), pp.1388-1394. ⟨10.1093/cid/ciy293⟩. ⟨pasteur-02565607⟩

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