title: Predictive Studies Suggest that the Risk for the Selection of Antibiotic Resistance by Biocides Is Likely Low in Stenotrophomonas maltophilia.
abstract: Biocides are used without restriction for several purposes. As a consequence, large amounts of biocides are released without any control in the environment, a situation that can challenge the microbial population dynamics, including selection of antibiotic resistant bacteria. Previous work has shown that triclosan selects Stenotrophomonas maltophilia antibiotic resistant mutants overexpressing the efflux pump SmeDEF and induces expression of this pump triggering transient low-level resistance. In the present work we analyze if two other common biocides, benzalkonium chloride and hexachlorophene, trigger antibiotic resistance in S. maltophilia. Bioinformatic and biochemical methods showed that benzalkonium chloride and hexachlorophene bind the repressor of smeDEF, SmeT. Only benzalkonium chloride triggers expression of smeD and its effect in transient antibiotic resistance is minor. None of the hexachlorophene-selected mutants was antibiotic resistant. Two benzalkonium chloride resistant mutants presented reduced susceptibility to antibiotics and were impaired in growth. Metabolic profiling showed they were more proficient than their parental strain in the use of some dipeptides. We can then conclude that although bioinformatic predictions and biochemical studies suggest that both hexachlorophene and benzalkonium chloride should induce smeDEF expression leading to transient S. maltophilia resistance to antibiotics, phenotypic assays showed this not to be true. The facts that hexachlorophene resistant mutants are not antibiotic resistant and that the benzalkonium chloride resistant mutants presenting altered susceptibility to antibiotics were impaired in growth suggests that the risk for the selection (and fixation) of S. maltophilia antibiotic resistant mutants by these biocides is likely low, at least in the absence of constant selection pressure.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (CSIC), Darwin 3, Cantoblanco, 28049-Madrid, Spain.
authors.forename: María Blanca
authors.initials: MB
authors.lastname: Sánchez
authors.affiliation: Dipartimento di Scienze delle Produzioni Agroalimentari e dell'Ambiente, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Decorosi
authors.affiliation: Dipartimento di Scienze delle Produzioni Agroalimentari e dell'Ambiente, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Viti
authors.affiliation: Department of Genetics, University of Leicester, Leicester, LE1 7RH, United Kingdom.
authors.forename: Marco Rinaldo
authors.initials: MR
authors.lastname: Oggioni
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (CSIC), Darwin 3, Cantoblanco, 28049-Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Martínez
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (CSIC), Darwin 3, Cantoblanco, 28049-Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Hernández
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001548:Benzalkonium Compounds / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods; D004202:Disinfectants / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006582:Hexachlorophene / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*
chemical_list: D001426:Bacterial Proteins; D001548:Benzalkonium Compounds; D004202:Disinfectants; D006582:Hexachlorophene