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PLoS One. 2013 Nov 18;8(11):e79499. doi: 10.1371/journal.pone.0079499. eCollection 2013.

DNA, cell wall and general oxidative damage underlie the tellurite/cefotaxime synergistic effect in Escherichia coli.

Author information

1
Laboratorio de Microbiología Molecular, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.

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.

PMID:
24260236
PMCID:
PMC3832599
DOI:
10.1371/journal.pone.0079499
[Indexed for MEDLINE]
Free PMC Article

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