DNA REPAIR MECHANISMS AND MUTAGENESIS IN Pseudomonas aeruginosa BETA-LACTAMS-RESPONSE

• Grant number: 16/18979-1
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: December 01, 2016
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Rodrigo da Silva Galhardo
• Grantee: Letícia Busato Migliorini
• Supervisor: Jesus Blazquez Gomez
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Consejo Superior de Investigaciones Científicas (CSIC), Spain
• Associated to the scholarship: 15/18886-0 - Role of DNA repair mechanisms in the response of Pseudomonas aeruginosa to antimicrobials ciprofloxacin and ceftazidime, BP.MS

Abstract

Pseudomonas aeruginosa is an important human opportunistic pathogen, responsible for the high mortality rates in patients with cystic fibrosis. This bacterium has great ability to adapt to adverse situations, which facilitates the establishment and persistence of infection. The inappropriate antibiotic therapy and contact with sub-inhibitory concentrations may cause the bacteria to respond in various ways. Among them, the activation of the SOS response and production of reactive oxygen species (ROS) which can lead to oxidative DNA damage, such as 8-oxoguanine (8-oxoG). Both the SOS response and the oxidative stress is associated mutagenesis procedures, which may contribute to the development of bacterial resistance. beta-lactam antibiotics such as Ceftazidime (CAZ), widely used in clinical practice, has been described as activating agents of the SOS response and oxidative stress inducers, being able to promote mutagenesis in P. aeruginosa PAO1. The data obtained so far by our research group in P. aeruginosa PA14, there was no increase in mutagenesis induced CAZ. In this sense, it is important to better elucidate these results and assess P. aeruginosa response to other beta-lactams, including Ticarcillin, Piperacillin, Cefepime and Carbenicillin. Therefore, this study polymerases role of SOS and involvement of oxidative stress is evaluated by Flow Cytometry. In addition, we will evaluate the frequency of mutants induced by beta-lactams in different strains with mutations in DNA repair genes of P. aeruginosa and some clinical isolates to verify that this mutagenesis occurs in a similar manner in these isolates. This study aims to clarify the P. aeruginosa response to beta-lactams, assisting in the development of more effective anti-microbial treatment strategies, thus reducing the risk of resistance development.