A 4.5-Year Within-Patient Evolution of a Colistin-Resistant Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Sequence Type 258 - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Clinical Infectious Diseases Année : 2018

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

Eric Farfour

Résumé

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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pasteur-02565607 , version 1 (06-05-2020)

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Paternité - Pas d'utilisation commerciale

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