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

Abstract

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 bla_CTX-M by PCR, which is a known mechanism for higher cephalosporin resistance. The isolate was further subjected to next-generation sequencing that identified bla_TEM-1B and bla_DHA-1 genes in association with qnrB4 and sul1. bla_TEM is a known gene coding for β-lactam resistance. In certain cases, overexpression of bla_TEM was reported to result in cephalosporin resistance. This suggests that the high cefixime MIC would have been contributed by overexpression of bla_TEM-1B. The bla_TEM-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 bla_TEM) 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.

Keywords: Bloodstream infection; Cephalosporin resistance; IncN plasmid; Salmonella Typhi; bla(TEM); qnr.