Combined genomic-proteomic approach in the identification of Campylobacter coli amoxicillin-clavulanic acid resistance mechanism in clinical isolates

Francis Deforet; Quentin Jehanne; Lucie Bénéjat; Johanna Aptel; Roxane Prat; Chloé Desbiolles; Astrid Ducournau; Marine Jauvain; Richard Bonnet; François Vandenesch; Jérôme Lemoine; Philippe Lehours

doi:10.3389/fmicb.2023.1285236

Combined genomic-proteomic approach in the identification of Campylobacter coli amoxicillin-clavulanic acid resistance mechanism in clinical isolates

Front Microbiol. 2023 Nov 9:14:1285236. doi: 10.3389/fmicb.2023.1285236. eCollection 2023.

Authors

Affiliations

¹ Institut des Sciences Analytiques, Université Claude Bernard Lyon 1, Lyon, France.
² Bacteriology Department, CHU de Bordeaux, National Reference Center for Campylobacters and Helicobacters, Bordeaux, France.
³ Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
⁴ Bordeaux Institute of Oncology, BRIC U1312, INSERM, Université de Bordeaux, Bordeaux, France.
⁵ Laboratoire Associé CNR de la Résistance aux Antibiotiques, CHU de Clermont-Ferrand, Clermont-Ferrand, France.

Abstract

Introduction: Aminopenicillins resistance among Campylobacter jejuni and Campylobacter coli strains is associated with a single mutation in the promoting region of a chromosomal beta-lactamase bla_OXA61, allowing its expression. Clavulanic acid is used to restore aminopenicillins activity in case of bla_OXA61 expression and has also an inherent antimicrobial activity over Campylobacter spp. Resistance to amoxicillin-clavulanic acid is therefore extremely rare among these species: only 0.1% of all Campylobacter spp. analyzed in the French National Reference Center these last years (2017-2022).

Material and methods: Whole genome sequencing with bioinformatic resistance identification combined with mass spectrometry (MS) was used to identify amoxicillin-acid clavulanic resistance mechanism in Campylobacters.

Results: A G57T mutation in bla_OXA61 promoting region was identified in all C. jejuni and C. coli ampicillin resistant isolates and no mutation in ampicillin susceptible isolates. Interestingly, three C. coli resistant to both ampicillin and amoxicillin-clavulanic acid displayed a supplemental deletion in the promoting region of bla_OXA61 beta-lactamase, at position A69. Using MS, a significant difference in the expression of Bla_OXA61 was observed between these three isolates and amoxicillin-clavulanic acid susceptible C. coli.

Conclusion: A combined genomics/proteomics approach allowed here to identify a rare putative resistance mechanism associated with amoxicillin-clavulanic acid resistance for C. coli.

Keywords: AMR; Campylobacter; amoxicillin-clavulanic acid; beta-lactamase; gene expression.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Open access funding provided by the French National Reference Center for Campylobacters and Helicobacters, Bordeaux, France. Financially supported by Santé Publique France (www.santepubliquefrance.fr).