Draft genome sequence of blaTEM-1-mediated cephalosporin-resistant Salmonella enterica serovar Typhi from bloodstream infection.

Enteric fever is a major cause of concern in developing countries across the globe. The primary choice of antibiotics remains fluoroquinolones, followed by cephalosporins. Resistance to third-generation cephalosporins is rarely reported in Salmonella enterica serovar Typhi. This study reports the whole genome sequence of an S. Typhi isolate resistant to cefixime [minimum inhibitory concentration (MIC)=512μg/mL] by microbroth dilution. Interestingly, the isolate was negative for the cephalosporin resistance gene blaCTX-M by PCR, which is a known mechanism for higher cephalosporin resistance. The isolate was further subjected to next-generation sequencing that identified blaTEM-1B and blaDHA-1 genes in association with qnrB4 and sul1. blaTEM is a known gene coding for β-lactam resistance. In certain cases, overexpression of blaTEM was reported to result in cephalosporin resistance. This suggests that the high cefixime MIC would have been contributed by overexpression of blaTEM-1B. The blaTEM-1B gene was found to be associated with a promoter Px with -35 and -10 regions as TTAATA and TAAAGT, respectively. The promoter regions were unique, but the -10 region was similar to that found in Pa/Pb (previously reported promoter for blaTEM) with a single nucleotide change. In addition, an IncN plasmid was identified, which is usually reported in association with the most prevalent extended-spectrum β-lactamase (ESBL), metallo- and non-metallo-carbapenemase, and plasmid-mediated quinolone resistance (PMQR) genes. Plasmids such as IncN might possibly confer resistance and enhance spread. It is imperative to continuously monitor the drug resistance profile and evolving genetic elements.