Nicolas Kieffer1, Stefan Ebmeyer1, D G Joakim Larsson2. 1. Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden; Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 2. Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden; Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: joakim.larsson@fysiologi.gu.se.
Abstract
OBJECTIVES: Elucidating the recent evolutionary history of clinically important antibiotic resistance genes may inform measures to delay the future emergence of additional resistance genes in clinics. This study investigated the recent origin of blaAIM-1, a metallo-β-lactamase gene found in Pseudomonas aeruginosa, and the possible role of ISCR15 in its mobilisation and transfer into clinical species. METHODS: Comparative genomics were used to identify the recent origin of blaAIM. Mobilisation attempts were performed under different conditions by cloning ISCR15 and the blaAIM-1-like gene in Escherichia coli. RESULTS: Several blaAIM-1 homologues were identified in the Pseudoxanthomonas genus, with conserved synteny of the locus between species and absence of elements associated with mobility. The closest AIM-1 homologue (97.7% amino acid identity) was found in a Pseudoxanthomonas mexicana (P. mexicana) strain. Cloning the blaAIM-like gene in Escherichia coli resulted in high resistance towards carbapenems. While blaAIM-1 is surrounded by ISCR15 elements in clinical strains, in vitro experiments failed to demonstrate their role as mobilising elements. CONCLUSIONS: This study presents evidence that P. mexicana, an environmental species occasionally associated with infections, is the origin of the B3 metallo-β-lactamase AIM-1. The presence of terIS, a plausible recognition site for ISCR15, in other parts of the P. mexicana genome suggests a more complex and yet not understood mobilisation mechanism.
OBJECTIVES: Elucidating the recent evolutionary history of clinically important antibiotic resistance genes may inform measures to delay the future emergence of additional resistance genes in clinics. This study investigated the recent origin of blaAIM-1, a metallo-β-lactamase gene found in Pseudomonas aeruginosa, and the possible role of ISCR15 in its mobilisation and transfer into clinical species. METHODS: Comparative genomics were used to identify the recent origin of blaAIM. Mobilisation attempts were performed under different conditions by cloning ISCR15 and the blaAIM-1-like gene in Escherichia coli. RESULTS: Several blaAIM-1 homologues were identified in the Pseudoxanthomonas genus, with conserved synteny of the locus between species and absence of elements associated with mobility. The closest AIM-1 homologue (97.7% amino acid identity) was found in a Pseudoxanthomonas mexicana (P. mexicana) strain. Cloning the blaAIM-like gene in Escherichia coli resulted in high resistance towards carbapenems. While blaAIM-1 is surrounded by ISCR15 elements in clinical strains, in vitro experiments failed to demonstrate their role as mobilising elements. CONCLUSIONS: This study presents evidence that P. mexicana, an environmental species occasionally associated with infections, is the origin of the B3 metallo-β-lactamase AIM-1. The presence of terIS, a plausible recognition site for ISCR15, in other parts of the P. mexicana genome suggests a more complex and yet not understood mobilisation mechanism.