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

Abstract

The increasing resistance to cephalosporins in Salmonella poses a serious threat to public health. In our previous study, the blaCTX-M-101 gene, a new blaCTX-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 blaCTX-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 μg/mL), cefotaxime (MIC = 256 μg/mL), and cefepime (MIC = 16 μg/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 blaCTX-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 blaCTX-M-101 gene was located on an IncI1-Iα 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, blaCTX-M-101, and orf477 in p14523A. ISEcp1-mediated transposition was likely to play a key role in the horizontal transfer of blaCTX-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.