Identification of a novel beta-lactamase, Axy_1, involved 1 in resistance 2 towards carbapenem in a clinical isolate of Achromobacter xylosoxidans

We analysed the proteome of two clinical isolates of Achromobacter xylosoxidans from the same patient, with the latter showing meropenem resistance and being isolated during unsuccessful meropenem treatment. This analysis revealed Axy_1, a class A beta-lactamase that causes resistance against imipenem and meropenem. High Axy-1 protein levels were observed in the resistant strain while Axy_1 was not found in the susceptible strain. Both isolates were sequenced, and a single mutation difference was found discriminating both genomes, thereby confirming clonality of the isolates. The mutation was found in a repressor that might also act on Axy_1 which potentially may result in higher expression. Axy_1’s activity towards carbapenems was demonstrated in vitro by expression in E. coli and performing susceptibility testing. This previously unreported activity can have greater implications for class A beta-lactamases. Further investigation into the underlying mechanism could allow the identification of similar beta-lactamases