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SOS response and bacterial resistance in Pseudomonas aeruginosa


The SOS response is a cellular mechanism of protection against genotoxic stress. In addition to regulating the expression of DNA repair genes, this cellular response also induces mutagenesis, because of the regulation of error prone DNA polymerases. Several classes of antimicrobials are inducers of the SOS response, and therefore can accelerate the emergence of mutants in bacterial populations, indirectly favoring the emergence of resistance. The objective of this project is to study the induction of the SOS response by the antimicrobial ciprofloxacin in the pathogen Pseudomonas aeruginosa, seeking to understand its occurrence in clinical isolates. We also intend to uncover the physiological role of genes belonging to this regulon. Through a genetic screening, we will identify cellular factors that affect the expression of the SOS response by ciprofloxacin. Finally, we intend to uncover the molecular basis of an antagonistic interaction between ciprofloxacin and amikacin with respect to the induction of the SOS response, through transcriptomic studies. In summary, we will seek a better global understanding of the physiology of the SOS response in P. aeruginosa, and its activation in clinical isolates in response to ciprofloxacin. (AU)

Articles published in Pesquisa FAPESP Magazine about the research grant:
A theory in motion