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

Nunes, Alexandra; Oleastro, Monica; Alves, Frederico; Liassine, Nadia; Lowe, David M; Benejat, Lucie; Ducounau, Astrid; ... Philippe, Lehours; + view all (2023) Recurrent Campylobacter jejuni Infections with In Vivo Selection of Resistance to Macrolides and Carbapenems: Molecular Characterization of Resistance Determinants. Microbiology Spectrum , 11 (4) 10.1128/spectrum.01070-23. Green open access

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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 b-strands 5 and 6 and forms a constriction zone involved in Ca21 binding. The isolates presenting the highest MIC to ertapenem exhibited an extra nonsynonymous mutation (G167AjGly56Asp) 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.

Type: Article
Title: Recurrent Campylobacter jejuni Infections with In Vivo Selection of Resistance to Macrolides and Carbapenems: Molecular Characterization of Resistance Determinants
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/spectrum.01070-23
Publisher version: https://doi.org/10.1128/spectrum.01070-23
Language: English
Additional information: © 2023 Nunes et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: Campylobacter jejuni recurrent infection, immunocompromised patients, macrolide resistance, high-level carbapenem resistance, major porin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10178930
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