title: DNA, cell wall and general oxidative damage underlie the tellurite/cefotaxime synergistic effect in Escherichia coli.
abstract: The constant emergence of antibiotic multi-resistant pathogens is a concern worldwide. An alternative for bacterial treatment using nM concentrations of tellurite was recently proposed to boost antibiotic-toxicity and a synergistic effect of tellurite/cefotaxime (CTX) was described. In this work, the molecular mechanism underlying this phenomenon is proposed. Global changes of the transcriptional profile of Escherichia coli exposed to tellurite/CTX were determined by DNA microarrays. Induction of a number of stress regulators (as SoxS), genes related to oxidative damage and membrane transporters was observed. Accordingly, increased tellurite adsorption/uptake and oxidative injuries to proteins and DNA were determined in cells exposed to the mixture of toxicants, suggesting that the tellurite-mediated CTX-potentiating effect is dependent, at least in part, on oxidative stress. Thus, the synergistic tellurite-mediated CTX-potentiating effect depends on increased tellurite uptake/adsorption which results in damage to proteins, DNA and probably other macromolecules. Our findings represent a contribution to the current knowledge of bacterial physiology under antibiotic stress and can be of great interest in the development of new antibiotic-potentiating strategies.
authors.affiliation: Laboratorio de Microbiología Molecular, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Molina-Quiroz
authors.forename: David E
authors.initials: DE
authors.lastname: Loyola
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Muñoz-Villagrán
authors.forename: Raquel
authors.initials: R
authors.lastname: Quatrini
authors.forename: Claudio C
authors.initials: CC
authors.lastname: Vásquez
authors.forename: José M
authors.initials: JM
authors.lastname: Pérez-Donoso
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects*; D013691:Tellurium / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C026660:tellurous acid; D002439:Cefotaxime; D013691:Tellurium