WGS for surveillance of antimicrobial resistance: A pilot study to detect the prevalence and mechanism of resistance to azithromycin in a UK population of non-typhoidal Salmonella

Satheesh Nair, Philip Ashton, Michel Doumith, Steve Connell, Anais Painset, Solomon Mwaigwisya, Gemma Langridge, Elizabeth Depinna, Gauri Godbole, Martin Day

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

WGS and phenotypic methods were used to determine the prevalence of azithromycin resistance in Salmonella enterica isolates from the UK and to identify the underlying mechanisms of resistance. Methods: WGS by Illumina HiSeq was carried out on 683 Salmonella spp. isolates. Known genes associated with azithromycin resistance were detected by WGS using a mapping-based approach. Macrolide resistance determinants were identified and the genomic context of these elements was assessed by various bioinformatics tools. Susceptibility testing was in accordance with EUCAST methodology (MIC ≤ 16 mg/L). Results: Fifteen isolates of non-typhoidal Salmonella enterica belonging to serovars Salmonella Blockley, Salmonella Typhimurium, Salmonella Thompson, Salmonella Ridge and Salmonella Kentucky showed resistance or decreased susceptibility to azithromycin (from 6 to.16 mg/L) due to the presence of macrolide resistance genes mphA, mphB or mefB. These genes were either plasmid or chromosomally mediated. Azithromycinresistant Salmonella Blockley isolates harboured a macrolide inactivation gene cluster, mphA-mrx-mphr(A), within a novel Salmonella azithromycin resistance genomic island (SARGI) determined by MinION sequencing. This is the first known chromosomally mediated mphA gene cluster described in salmonellae. Phylogenetic analysis and epidemiological information showed that mphA Salmonella Blockley isolates were not derived from a single epidemiologically related event. The azithromycin MICs of the 15 Salmonella spp. isolates showed that the presence of the mphA gene was associated with MIC ≥ 16 mg/L, while the presence of mefB or mphB was not. Conclusions: Azithromycin resistance due to acquisition of known macrolide resistance genes was seen in four different Salmonella serovars and can be either plasmid-encoded or chromosomally encoded.

Original languageEnglish
Pages (from-to)3400-3408
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number12
DOIs
Publication statusPublished - Dec 2016

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