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Staphylococcus saprophyticus Causing Infections in Humans Is Associated with High Resistance to Heavy Metals

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  1. Danish Whole-Genome-Sequenced Candida albicans and Candida glabrata Samples Fit into Globally Prevalent Clades

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Staphylococcus saprophyticus From Clinical and Environmental Origins Have Distinct Biofilm Composition

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Opeyemi U Lawal
  • Maria J Fraqueza
  • Peder Worning
  • Ons Bouchami
  • Mette D Bartels
  • Luisa Goncalves
  • Paulo Paixão
  • Elsa Goncalves
  • Cristina Toscano
  • Joanna Empel
  • Malgorzata Urbaś
  • Maria A Domínguez
  • Henrik Westh
  • Hermínia de Lencastre
  • Maria Miragaia
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Staphylococcus saprophyticus is a common pathogen of the urinary tract, a heavy metal-rich environment, but information regarding its heavy metal resistance is unknown. We investigated 422 S. saprophyticus isolates from human infection and colonization/contamination, animals, and environmental sources for resistance to copper, zinc, arsenic, and cadmium using the agar dilution method. To identify the genes associated with metal resistance and assess possible links to pathogenicity, we accessed the whole-genome sequence of all isolates and used in silico and pangenome-wide association approaches. The MIC values for copper and zinc were uniformly high (1,600 mg/liter). Genes encoding copper efflux pumps ( copA, copB, copZ, mco, and csoR) and zinc transporters ( zinT, czrAB, znuBC, and zur) were abundant in the population (20 to 100%). Arsenic and cadmium showed various susceptibility levels. Genes encoding the ars operon ( arsRDABC), an ABC transporter and a two-component permease, were linked to resistance to arsenic (MICs ≥ 1,600 mg/liter; 14% [58/422]; P  < 0.05). At least three cad genes ( cadA or cadC and cadD-cadX or czrC) and genes encoding multidrug efflux pumps and hyperosmoregulation in acidified conditions were associated with resistance to cadmium (MICs ≥ 200 mg/liter; 20% [85/422]; P < 0.05). These resistance genes were frequently carried by mobile genetic elements. Resistance to arsenic and cadmium were linked to human infection and a clonal lineage originating in animals ( P < 0.05). Altogether, S. saprophyticus was highly resistant to heavy metals and accumulated multiple metal resistance determinants. The highest arsenic and cadmium resistance levels were associated with infection, suggesting resistance to these metals is relevant for S. saprophyticus pathogenicity.

Original languageEnglish
Article numbere0268520
JournalAntimicrobial Agents and Chemotherapy
Issue number7
Publication statusPublished - 17 Jun 2021

    Research areas

  • Arsenic, Cadmium, Copper, Environment, Heavy metals, Metal resistance, Metal resistance determinants, Pan-GWAS, Staphylococcus saprophyticus, Urinary tract infection, Whole-genome sequencing, Zinc

ID: 65429491