title: 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.
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.
  
  
  
  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).
  
  
  
  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. Azithromycin-resistant 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.
  
  
  
  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.
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK satheesh.nair@phe.gov.uk.
authors: Satheesh
authors: S
authors: Nair
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Philip
authors: P
authors: Ashton
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Michel
authors: M
authors: Doumith
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Steve
authors: S
authors: Connell
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Anais
authors: A
authors: Painset
authors: Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors: Solomon
authors: S
authors: Mwaigwisya
authors: Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors: Gemma
authors: G
authors: Langridge
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Elizabeth
authors: E
authors: de Pinna
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Gauri
authors: G
authors: Godbole
authors: Gastrointestinal Bacteria Reference Unit, Public Health England, London NW9 5EQ, UK.
authors: Martin
authors: M
authors: Day
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D062665:Epidemiological Monitoring; D005260:Female; D005798:Genes, Bacterial; D044404:Genomic Islands; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D005810:Multigene Family; D010802:Phylogeny; D010865:Pilot Projects; D015995:Prevalence; D012189:Retrospective Studies; D012475:Salmonella / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D012480:Salmonella Infections / Q000453:epidemiology / Q000382:microbiology*; D017422:Sequence Analysis, DNA / Q000379:methods; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin