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 Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2018
• End date: September 30, 2022
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Luis Eduardo Soares Netto
• Grantee: Helena Gabriela Turano Gomes
• Host 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.

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)

GOMES, FERNANDO; TURANO, HELENA; RAMOS, ANGELICA; NETTO, LUIS E. S.. Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 173, JUL 2021. (17/09443-3, 13/07937-8, 17/23839-7)