Emergence of a Hybrid IncI1-Iα Plasmid-Encoded blaCTX-M-101 Conferring Resistance to Cephalosporins in Salmonella enterica Serovar Enteritidis

The increasing resistance to cephalosporins in Salmonella poses a serious threat to public health. In our previous study, the bla(CTX-M-101) gene, a new bla(CTX-M) variant, was first reported in Salmonella enterica serovar Enteritidis (S. Enteritidis). Here, we further analyzed the genome characterization, transferability, and resistance mechanism of one S. Enteritidis isolate (SJTUF14523) carrying bla(CTX-M-101) from an outpatient in 2016 in Xinjiang, China. This strain was a multidrug resistance (MDR) isolate and exhibited resistance to ceftazidime (MIC = 64 mu g/mL), cefotaxime (MIC = 256 mu g/mL), and cefepime (MIC = 16 mu g/mL). Phylogenetic analysis revealed that SJTUF14523 had a close relationship to another S. Enteritidis isolate from the United States. In the presence of plasmid p14523A, there were 8- and 2133-fold increases in the MICs of cephalosporins in Escherichia coli C600 in the conjugation. Gene cloning results indicated that bla(CTX-M-101) was the decisive mechanism leading to ceftazidime and cefotaxime resistance that could make the MICs break through the resistance breakpoint. Plasmid sequencing revealed that the bla(CTX-M-101) gene was located on an IncI1-Iff transferable plasmid (p14523A) that was 85,862 bp in length. Sequence comparison showed that p14523A was a novel hybrid plasmid that might have resulted from the interaction between a homologous region. Furthermore, we found a composite transposon unit composed of ISEcp1, bla(CTX-M-101), and orf 477 in p14523A. ISEcp1-mediated transposition was likely to play a key role in the horizontal transfer of bla(CTX-M-101) among plasmids in S. Enteritidis. Collectively, these findings underline further challenges in the prevention and control of antibiotic resistance posed by new CTX-M-101-like variants in Salmonella.

Automated summary

The increasing resistance to cephalosporins in Salmonella is a serious threat to public health. A new bla(CTX-M) variant, bla(CTX-M-101), was first reported in Salmonella enterica serovar Enteritidis. Further analysis of isolate SJTUF14523 carrying bla(CTX-M-101) revealed its genome characterization, transferability, and resistance mechanism. This multidrug resistance isolate exhibited high resistance to ceftazidime, cefotaxime, and cefepime. The presence of plasmid p14523A resulted in increased resistance to cephalosporins in Escherichia coli C600. Gene cloning and plasmid sequencing showed that bla(CTX-M-101) was located on a transferable plasmid, p14523A, and a composite transposon unit was found in this plasmid. These findings emphasize the challenges posed by new CTX-M-101-like variants in Salmonella and the need for prevention and control of antibiotic resistance.