TY - JOUR
T1 - Staphylococcus saprophyticus causing infections in humans is associated with high resistance to heavy metals
AU - Lawal, Opeyemi U.
AU - Fraqueza, Maria J.
AU - Worning, Peder
AU - Bouchami, Ons
AU - Bartels, Mette D.
AU - Goncalves, Luisa
AU - Paixão, Paulo
AU - Goncalves, Elsa
AU - Toscano, Cristina
AU - Empel, Joanna
AU - Urbaś, Malgorzata
AU - Domínguez, Maria A.
AU - Westh, Henrik
AU - de Lencastre, Hermínia
AU - Miragaia, Maria
N1 - Funding Information:
O.U.L. was supported by PhD grants from the Fundação para a Ciência e Tecnologia (FCT) PD/BD/113992/2015. This work was partially supported by project PTDC/CVT-CVT/ 29510/2017 from Fundação para a Ciência e Tecnologia, projects LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) and UID/Multi/04378/2019) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI), by ONEIDA project (LISBOA-01-0145-FEDER-016417) cofunded by FEEI (Fundos Europeus Estruturais e de Investimento) from Programa Operacional Regional Lisboa2020, and by national funds through FCT, Operacional Competitividade e Internacionalização, Programa Operacional Regional de Lisboa (FEDER), and Fundação para a Ciência e a Tecnologia.
Funding Information:
O.U.L. and O.B. performed the isolation. O.U.L. performed the phenotypic experiments and bioinformatics analysis. O.U.L., H.W., P.W., and M.D.B. performed the sequencing of the isolates. O.U.L. and M.M. carried out the data analysis and interpretation and wrote the first draft of the manuscript. O.U.L. and M.M. revised the manuscript. M.J.F., L.G., P.P., E.G., C.T., J.E., M.U., H.d.L., H.W., and M.D.B. provided the isolates. M.J.F., L.G., P.P., E.G., C.T., J.E., M.U., H.d.L., H.W., P.W., and M.D.B. were involved in manuscript revision. All authors read and approved the final manuscript. O.U.L. was supported by PhD grants from the Funda??o para a Ci?ncia e Tecnologia (FCT) PD/BD/113992/2015. This work was partially supported by project PTDC/CVT-CVT/ 29510/2017 from Funda??o para a Ci?ncia e Tecnologia, projects LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) and UID/Multi/04378/2019) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionaliza??o (POCI), by ONEIDA project (LISBOA-01-0145-FEDER- 016417) cofunded by FEEI (Fundos Europeus Estruturais e de Investimento) from Programa Operacional Regional Lisboa2020, and by national funds through FCT, Operacional Competitividade e Internacionaliza??o, Programa Operacional Regional de Lisboa (FEDER), and Funda??o para a Ci?ncia e a Tecnologia. We declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher Copyright:
Copyright © 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - Arsenic
KW - Cadmium
KW - Copper
KW - Environment
KW - Heavy metals
KW - Metal resistance
KW - Metal resistance determinants
KW - Pan-GWAS
KW - Staphylococcus saprophyticus
KW - Urinary tract infection
KW - Whole-genome sequencing
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85108276227&partnerID=8YFLogxK
U2 - 10.1128/AAC.02685-20
DO - 10.1128/AAC.02685-20
M3 - Article
C2 - 33941519
AN - SCOPUS:85108276227
SN - 0066-4804
VL - 65
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 7
M1 - e02685-20
ER -
