Abstract
ABSTRACT Ceftriaxone and ciprofloxacin are the drugs of choice in treatment of invasive Salmonella infections. This study discovered a novel type of plasmid, pSa44-CIP-CRO, which was recovered from a S. London strain isolated from meat product and comprised genetic determinants that encoded resistance to both ciprofloxacin and ceftriaxone. This plasmid could be resolved into two daughter plasmids and co-exist with such daughter plasmids in a dynamic form in Salmonella; yet it was only present as a single plasmid in Escherichia coli. One daughter plasmid, pSa44-CRO, was found to carry the bla CTX-M-130 gene, which encodes resistance to ceftriaxone, whereas the other plasmid, pSa44-CIP, carried multiple PMQR genes such as qnrB6-aac(6’)-Ib-cr, which mediated resistance to ciprofloxacin. These two daughter plasmids could be integrated into one single plasmid through ISPa40 mediated homologous recombination. Mouse infection and treatment experiments showed that carriage of plasmid, pSa44-CIP-CRO by S. typhimurium led to the impairment of treatment by ciprofloxacin or cefitiofur, a veterinary drug with similar properties as ceftriaxone. In conclusion, dissemination of such conjugative plasmids impairs current choices of treatment for life-threatening Salmonella infection and hence constitutes a serious public health threat.
Highlights
Salmonella is a leading cause of food-borne illness worldwide [1]
Conjugation experiments showed that ceftriaxone and ciprofloxacin resistance phenotype of Sa44 could be transferred to E. coli J53, while those of other two strains could not
Bacterial resistance to fluoroquinolones such as ciprofloxacin was historically known to be mediated by target gene mutations
Summary
Salmonella is a leading cause of food-borne illness worldwide [1]. Intestinal salmonellosis is usually selflimiting and resolves in five to seven days without antibiotic treatment. When infection spreads beyond the intestinal tract, appropriate antimicrobial therapy (e.g. ciprofloxacin in adults and ceftriaxone in children) can be lifesaving [2]. The increasing use of fluoroquinolone and cephalosporins in livestock for control and treatment of infectious diseases have caused a steady increase in the incidence of resistance to these two types of antibiotics. Resistance to ceftriaxone in Salmonella appears to be slowly increasing, reaching a rate of around 3∼4%, but remained stable in the past few years [7,8]. The rate of resistance to ciprofloxacin has increased dramatically in both clinical and food isolates in various countries in recent years, in China and the adjacent areas [9]
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