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

Autor: Nunes A; Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge (INSA), Lisbon, Portugal.; Faculty of Veterinary Medicine, Lusófona University, Lisbon, Portugal., Oleastro M; Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge (INSA), Lisbon, Portugal., Alves F; Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge (INSA), Lisbon, Portugal., Liassine N; Laboratoire Dianalabs, Geneva, Switzerland., Lowe DM; University College London, London, United Kingdom., Benejat L; French National Reference Centre for Campylobacters and Helicobacters, Bordeaux Hospital University Centre, Bordeaux, France., Ducounau A; French National Reference Centre for Campylobacters and Helicobacters, Bordeaux Hospital University Centre, Bordeaux, France., Jehanne Q; French National Reference Centre for Campylobacters and Helicobacters, Bordeaux Hospital University Centre, Bordeaux, France., Borges V; Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge (INSA), Lisbon, Portugal., Gomes JP; Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge (INSA), Lisbon, Portugal.; Faculty of Veterinary Medicine, Lusófona University, Lisbon, Portugal., Godbole G; UK Health Security Agency, London, United Kingdom., Philippe L; French National Reference Centre for Campylobacters and Helicobacters, Bordeaux Hospital University Centre, Bordeaux, France.; University of Bordeaux, INSERM, Bordeaux Institute of Oncology, Bordeaux, France.
Jazyk: angličtina
Zdroj: Microbiology spectrum [Microbiol Spectr] 2023 Aug 17; Vol. 11 (4), pp. e0107023. Date of Electronic Publication: 2023 Jun 26.
DOI: 10.1128/spectrum.01070-23
Abstrakt: 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 Ca 2+ 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 por A. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE