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Investigation of the S8 pyocin bactericidal activity: new perspectives for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa strains

Grant number: 17/23839-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2018
Effective date (End): April 30, 2020
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Luis Eduardo Soares Netto
Grantee:Helena Gabriela Turano Gomes
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that can cause different infections in humans. The emergence and spread of multidrug-resistant strains (MRs) caused high levels of morbidity and mortality. Bacterial resistance has been extensively documented and now represents a global threat to mankind. Due to the absence of efficient antimicrobials against P. aeruginosa MRs, the development of new therapeutic approaches is required. Recent studies have shown that pyocins have potent bactericidal activity against P. aeruginosa, but their efficacy against MR strains has been poorly explored. Pyocins are proteinaceous toxins produced by P. aeruginosa under certain stressful conditions that can take part in intra-species competition. During my PhD program, I demonstrated that the S8 pyocin produced by the P. aeruginosa strain (ET02), isolated from the human intestinal microbiota, showed potent bactericidal activity against thirteen P. aeruginosa strains producing clinically important ²-lactamases (SPM- 1, GIM-1, VIM-1, IMP-1, KPC-2 and GES-5). However, mechanisms underlying these processes are still elusive. In this project, we intend to employ structural, biochemical, microbiological and virulence assays to better understand the bactericidal action of pyocins. Emphasis will be given to the S8 pyocin, whose studies began during my PhD program. Eventually other pyocins may be characterized and compared with S8 pyocin. Strategies to achieve these goals are described below.