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Genomic and genetic analysis of SOS response induction in Pseudomonas aeruginosa

Grant number: 20/12744-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2020
Effective date (End): October 31, 2024
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Cooperation agreement: Netherlands Organisation for Scientific Research (NWO)
Principal researcher:Rodrigo da Silva Galhardo
Grantee:Renatta Santos de Oliveira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg), AP.TEM

Abstract

In Pseudomonas aeruginosa, an opportunistic pathogen very important in public health, the SOS response contributes to the emergence of resistance mutations, in addition to promoting DNA repair and cell survival. This phenomenon occurs through the activation of this regulon in response to damage to bacterial DNA, which includes oxidative damage, damage caused by UV light and breaks caused by the inhibition of DNA topoisomerases under ciprofloxacin antimicrobial treatments. As part of the SOS response, there is an increase in expression of low-fidelity DNA polymerases, which introduce mutations into the genome as a result of its mechanism of action. However, little is known about the nature and extent of this mutagenesis in bacterial DNA. Thereby, we intend to use a genomic sequencing approach to determine the number and type of mutations that are introduced into the genome under these conditions. Interestingly, two other P. aeruginosa regulons, controlled by the AlpR and PrtR repressors, homologues of the SOS LexA response controller, also respond to DNA damage. These control genes are involved in cell autolysis and the production of bacteriocins known as pyocines. Many strains of P. aeruginosa produce such pyocines. Thus, antagonistic responses are induced by DNA damage: protective mechanisms controlled by the canonical SOS (LexA), and responses that lead to cell lysis, where the individual sacrifices himself in favor of the population. It is not yet known how the other responses affect the biological manifestations of SOS, such as mutagenesis. The effect of the expression of these other regulons on the SOS response will also be studied in this project. (AU)