SOS response and bacterial resistance in Pseudomonas aeruginosa

• Grant number: 17/22430-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2018
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Rodrigo da Silva Galhardo
• Grantee: Rodrigo da Silva Galhardo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/06566-2 - DNA polymerases and antibiotic-induced mutagenesis in Pseudomonas aeruginosa, BP.TT

Abstract

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)