ACT-107, a novel variant of AmpC β-lactamase from Enterobacter huaxiensis isolated from Neotropical leaf frog (Phyllomedusa distincta) inhabiting the Brazilian Atlantic Forest

Author(s)

Becerra, Johana ; Araujo, Gabriel G. ; Vasquez-Ponce, Felipe ; Lamadrid-Feris, Faride ; Lincopan, Nilton

• Document type: Journal article
• Source: JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE; v. 33, p. 7-pg., 2023-06-08.

Abstract

Objectives: The aim of this study was to characterise a broad-spectrum cephalosporin-resistant AmpC-positive Enterobacter huaxiensis colonising the skin of a Neotropical frog (Phyllomedusa distincta) inhabiting the Brazilian Atlantic Forest. Methods: During a genomic surveillance study of antimicrobial resistance, we screened skin samples from P. distincta. Gram-negative bacteria growing on MacConkey agar plates supplemented with 2 mu g/mL ceftriaxone were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. A cephalosporin-resistant E. huaxiensis was sequenced using the Illumina NextSeq platform. Genomic data were analysed using bioinformatics tools, whereas AmpC beta-lactamase was characterised in depth by comparative analysis of amino acids, in silico modelling, and analysis of susceptibility to beta-lactam antibiotics and combinations of beta-lactamase inhibitors. Results: Whole-genome sequencing analysis revealed a novel variant of AmpC beta-lactamase belonging to the ACT family, designated ACT-107 by NCBI. This variant contains 12 novel amino acid mutations within the ACT family, 5 in the signal peptide sequence (Ile2, Met14, Tyr16, Gly18 and Thr20), and 7 in the mature protein (Gln22, His43, Cys60, Thr157, Glu225, Ala252 and Asn310). In silico modelling showed that substitutions occurring in the mature chain are localised in the solvent-accessible surface of the protein, where they are not expected to affect the beta-lactamase activity, as observed in the resistance profile. Strikingly, 'not designated' ACT variants from E. huaxiensis were clustered ( > 96% identity) with ACT-107. Conclusion: Since E. huaxiensis has been isolated from human infection, ACT-107 requires surveillance and the attention of clinicians. (C) 2023 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ ) (AU)

• FAPESP's process: 20/08224-9 - OneBR (One Health Brazilian Resistance): integrated genomic database for surveillance, diagnosis, management and treatment of antimicrobial resistance in the human-animal-environment interface, in Brazil
• Grantee: Nilton Erbet Lincopan Huenuman
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/16320-7 - Impacts of climate/environmental change on the fauna: an integrative approach
• Grantee: Carlos Arturo Navas Iannini
• Support Opportunities: Research Program on Global Climate Change - Thematic Grants
• FAPESP's process: 18/21076-9 - Structure of the Xanthomonas citri type IV pilus secretin
• Grantee: Gabriel Guarany de Araujo
• Support Opportunities: Scholarships in Brazil - Doctorate