Role of DNA repair mechanisms in the response of Pseudomonas aeruginosa to antimicrobials ciprofloxacin and ceftazidime

• Grant number: 15/18886-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2015
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Rodrigo da Silva Galhardo
• Grantee: Letícia Busato Migliorini
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 16/18979-1 - DNA REPAIR MECHANISMS AND MUTAGENESIS IN Pseudomonas aeruginosa BETA-LACTAMS-RESPONSE, BE.EP.MS

Abstract

The high incidence of multidrug-resistant Pseudomonas aeruginosa isolates is of extreme concern for the medical and scientific community. It is related to high mortality in patients with cystic fibrosis. Inappropriate antimicrobial therapy and the presence of sub-lethal concentrations of drugs in the environment has been associated with the induction of mutagenesis, bacterial resistance, and selection of mutants adapted to stress. Mutations may be caused by exogenous agents such as antimicrobials or as a result of metabolism when the organism is exposed to a stress. The antibiotics ciprofloxacin and ceftazidime, which directly or indirectly can cause DNA damage, can activate the SOS system, which expresses genes encoding the low-fidelity polymerases. In this case, DNA replication continues even in the presence of injury genome, in a process that can cause mutations. The imuAB dnaE2 operon is present in P. aeruginosa, and has been related to increased mutation rates and drug resistance in Caulobacter crescentus. The function of this operon has not been evaluated in P. aeruginosa. Therefore, it is important to study the nature of the mutagenesis mechanisms induced by antibiotics Ciprofloxacin and Ceftazidime, assessing the SOS response to beta-lactams and the function of error-prome DNA polymerases. Other DNA repair mechanisms will also be investigated. These studies involve the identification of targets for drug design that may increase the efficacy of treatment or reducing the risk of developing resistance.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MIGLIORINI, LETICIA BUSATO; BRUGGEMANN, HOLGER; DE SALES, ROMARIO OLIVEIRA; MARIKO KOGA, PAULA CELIA; DE SOUZA, ANDREA VIEIRA; VALLE MARTINO, MARINES DALLA; GALHARDO, RODRIGO S.; SEVERINO, PATRICIA. Mutagenesis Induced by Sub-Lethal Doses of Ciprofloxacin: Genotypic and Phenotypic Differences Between the Pseudomonas aeruginosa Strain PA14 and Clinical Isolates. FRONTIERS IN MICROBIOLOGY, v. 10, JUL 10 2019. (15/18886-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MIGLIORINI, Letícia Busato. Role of DNA repair mechanisms in the response of Pseudomonas aeruginosa to the antimicrobials Ciprofloxacin and Ceftazidime.. 2017. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.