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

Autor: Eric Farfour, Rémy A. Bonnin, Isabelle Rosinski-Chupin, Philippe Glaser, Agnès B Jousset, Laurent Dortet, Delphine Girlich, Hélène Frech, Thierry Naas, Gaelle Cuzon, Nicolas Cabanel
Přispěvatelé: Centre National de Référence Associé de la Résistance aux Antibiotiques, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bicêtre, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS), Structure, Dynamique, Fonction Et Expression Des Beta-Lactamases À Large Spectre, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11)-Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Bordeaux (UB), CHI Poissy-Saint-Germain, Hôpital Foch [Suresnes], This work was supported by the Assistance Publique–Hôpitaux de Paris, Université Paris Sud (grant number EA 7361), LabEx Laboratoire d’Excellence en Recherche sur le Médicament et l’InnovationThérapeutique, supported by the French National Research Agency (grant number Agence Nationale de la Recherche [ANR]-10-LABX-33), by a project of ANR LabEx Integrative Biology of Emerging Infectious Diseases, and the Joint Program Initiative on Antimicrobial Resistance (grant number ANR-14-JAMR-0002)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-JAMR-0002,DesInMBL,Structure-guided design of pan inhibitors of metallo-ß-lactamases(2014), Centre National de Référence Associé de la Résistance aux Antibiotiques [Hôpital Bicêtre AP-HP] (CNRARA/Service de Microbiologie), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
MESH: Fatal Outcome
Klebsiella pneumoniae
MESH: Klebsiella pneumoniae
Respiratory chain
MESH: beta-Lactamases
Bacteremia
Drug resistance
phylogeny
Fatal Outcome
carrier
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
polycyclic compounds
Medicine
MESH: Bacteremia
MESH: Bacterial Proteins
MESH: Microbial Sensitivity Tests
biology
MESH: Polymorphism
Single Nucleotide

within-host evolution
Anti-Bacterial Agents
3. Good health
MESH: Klebsiella Infections
Infectious Diseases
NGS
Carrier State
MESH: Equipment Contamination
MESH: Carrier State
MESH: Whole Genome Sequencing
medicine.drug
Microbiology (medical)
MESH: Mutation
030106 microbiology
Virulence
Microbial Sensitivity Tests
MESH: Biofilms
Polymorphism
Single Nucleotide

beta-Lactamases
MESH: Endoscopy
MESH: Fimbriae
Bacterial

Microbiology
Evolution
Molecular

03 medical and health sciences
Antibiotic resistance
Bacterial Proteins
MESH: Anti-Bacterial Agents
Drug Resistance
Bacterial

MESH: Drug Resistance
Bacterial

Humans
MESH: Humans
Whole Genome Sequencing
Colistin
business.industry
Endoscopy
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology

MESH: Colistin
biochemical phenomena
metabolism
and nutrition

bacterial infections and mycoses
biology.organism_classification
medicine.disease
MESH: Male
Klebsiella Infections
KPC
Carriage
Biofilms
Fimbriae
Bacterial

Mutation
Equipment Contamination
business
Zdroj: Clinical Infectious Diseases
Clinical Infectious Diseases, Oxford University Press (OUP), 2018, 67 (9), pp.1388-1394. ⟨10.1093/cid/ciy293⟩
Clinical Infectious Diseases, 2018, 67 (9), pp.1388-1394. ⟨10.1093/cid/ciy293⟩
ISSN: 1537-6591
1058-4838
DOI: 10.1093/cid/ciy293
Popis: International audience; 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.
Databáze: OpenAIRE