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The mobile FOX AmpC beta-lactamases originated in Aeromonas allosaccharophila

Journal article
Authors Stefan Ebmeyer
Erik Kristiansson
D. G. Joakim Larsson
Published in International Journal of Antimicrobial Agents
Volume 54
Issue 6
Pages 798-802
ISSN 0924-8579
Publication year 2019
Published at Department of Mathematical Sciences
Centre for antibiotic resistance research, CARe
Institute of Biomedicine, Department of Infectious Medicine
Pages 798-802
Language en
Keywords Aeromonas, AmpC, Antibiotic resistance, FOX
Subject categories Biological Sciences


© 2019 The Authors Objective: It is important to understand the origins of antibiotic resistance genes so that risks associated with the emergence of novel resistance genes can be assessed and managed. The chromosomal ampC gene (CAV-1) of Aeromonas caviae (A. caviae) has been reported as the origin of mobile FOX cephalosporinases. The recent identification of A. caviae as the origin of MOX-2 cephalosporinases and the comparably great sequence divergence between FOX and MOX genes makes it unlikely that both genes arose from the same species. Therefore, this study investigated the origin of FOX cephalosporinases using large-scale genomics. Methods: Publicly available genomes and plasmids were searched for FOX-like genes. Synteny and nucleotide identities of the identified FOX-like genes and their genetic environments were compared and a phylogenetic tree was generated. Results: FOX-like genes were identified in > 230 Aeromonas genomes and in 46 Enterobacteriaceae isolates. Analysis of the genomic context of CAV-1 revealed a truncated insertion sequence directly upstream of the ampC gene. The chromosomal ampCs of A. caviae (n = 31) were 75–78% identical to CAV-1. In contrast, CAV-1, mobile FOX genes and their context were 95–98% similar to the chromosomal ampC-locus of Aeromonas allosaccharophila (A. allosaccharophila) (n = 6). The A. allosaccharophila ampCs formed a monophyletic branch with mobile FOX genes, whereas the A. caviae ampCs clustered with mobile MOX genes. Conclusions: These findings show that FOX cephalosporinases originate not in A. caviae, as previously reported, but in A. allosaccharophila, which is a fish pathogen. This finding agrees with the hypothesis that antibiotic use in aquaculture could have contributed to the emergence of FOX genes in human pathogens.

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