title: 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 blaCTX-Mby PCR, which is a known mechanism for higher cephalosporin resistance. The isolate was further subjected to next-generation sequencing that identified blaTEM-1Band blaDHA-1genes in association with qnrB4 and sul1. blaTEMis a known gene coding for β-lactam resistance. In certain cases, overexpression of blaTEMwas reported to result in cephalosporin resistance. This suggests that the high cefixime MIC would have been contributed by overexpression of blaTEM-1B. The blaTEM-1Bgene 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.
authors.affiliation: Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Naveen Kumar
authors.initials: NK
authors.lastname: Devanga Ragupathi
authors.affiliation: Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Dhiviya Prabaa
authors.initials: DP
authors.lastname: Muthuirulandi Sethuvel
authors.affiliation: Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Baby Abirami
authors.initials: BA
authors.lastname: Shankar
authors.affiliation: Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Elakkiya
authors.initials: E
authors.lastname: Munusamy
authors.affiliation: Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Anandan
authors.affiliation: Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India. Electronic address: vbalaji@cmcvellore.ac.in.
authors.forename: Balaji
authors.initials: B
authors.lastname: Veeraraghavan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia; D002511:Cephalosporins / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D016680:Genome, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D012485:Salmonella typhi / Q000235:genetics*; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1
keywords: Bloodstream infection; Cephalosporin resistance; IncN plasmid; Salmonella Typhi; bla(TEM); qnr