Recurrent Campylobacter jejuni Infections with In Vivo Selection of Resistance to Macrolides and Carbapenems: Molecular Characterization of Resistance Determinants

Autor: Alexandra Nunes, Mónica Oleastro, Frederico Alves, Nadia Liassine, David M. Lowe, Lucie Benejat, Astrid Ducounau, Quentin Jehanne, Vítor Borges, João Paulo Gomes, Gauri Godbole, Lehours Philippe
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Microbiology Spectrum, Vol 11, Iss 4 (2023)
Druh dokumentu: article
ISSN: 2165-0497
DOI: 10.1128/spectrum.01070-23
Popis: ABSTRACT We present two independent cases of recurrent multidrug-resistant Campylobacter jejuni infection in immunocompromised hosts and the clinical challenges encountered due to the development of high-level carbapenem resistance. The mechanisms associated with this unusual resistance for Campylobacters were characterized. Initial macrolide and carbapenem-susceptible strains acquired resistance to erythromycin (MIC > 256mg/L), ertapenem (MIC > 32mg/L), and meropenem (MIC > 32mg/L) during treatment. Carbapenem-resistant isolates developed an in-frame insertion resulting in an extra Asp residue in the major outer membrane protein PorA, within the extracellular loop L3 that connects β-strands 5 and 6 and forms a constriction zone involved in Ca2+ binding. The isolates presenting the highest MIC to ertapenem exhibited an extra nonsynonymous mutation (G167A|Gly56Asp) at PorA’s extracellular loop L1. IMPORTANCE Carbapenem susceptibility patterns suggest drug impermeability, related to either insertion and/or single nucleotide polymorphism (SNP) within porA. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.
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