Prior exposure of agriculture cephalosporin ceftiofur impaired conjugation ofbla(CTX-M-65)gene-bearing plasmid inSalmonellaSaintpaul

摘要

Aims Although a link between agricultural cephalosporin use and resistance inSalmonellahas been demonstrated with the drug ceftiofur, the underlying mechanism of the correlation is unclear. This study investigated the impact of ceftiofur exposure inS. Saintpaul on ceftriaxone resistance, the gene expression and the conjugative transfer of thebla(CTX-M-65)gene. Methods and Results Prior ceftiofur exposure caused a twofold increase in MIC from 1024 to 2048 mu g ml(-1)towards ceftriaxone and increased the enzymatic activity of Bla(CTX-M-65)2 center dot 2 folds from 3 center dot 46 to 7 center dot 67 nmol nitrocefin hydrolysed min(-1). A threefold upregulation in gene expression of thebla(CTX-M-65)gene was also observed. Donors exposed to ceftiofur subsequently demonstrated a 2 center dot 5-fold decrease in transfer efficiency. Conclusions Prior exposure ofS. Saintpaul to ceftiofur led to increased phenotypic resistance towards ceftriaxone while its ability to spread the cephalosporin resistance through conjugation, conversely, was impaired. Significance and Impact of the Study Findings from this study shed light on one possible mechanism in which agricultural cephalosporin exposure inSalmonellamay subsequently impact clinical treatment. The finding that cephalosporin exposure in donors may hinder the subsequent spread of resistance instead of aiding it up was counter-intuitive.