The interplay between the ECF sigma factor PA14_46810 and c-di-GMP on the biofilm of Pseudomonas aeruginosa

• Grant number: 20/10229-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2021
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Regina Lúcia Baldini
• Grantee: Henrique Iglesias Neves
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Bacterical infections caused by Pseudmonoas aeruginosa are a challenge for Medicine due the difficult of treatment. P. aeruginosa is intrinsically resistant to most antibiotics and grows as biofilms in chronic infections. Biofilms consist of cells embedded in a matrix of polysaccharides, proteins and DNA. Such biofilms are difficult to remove and represent a physical barrier that protects the bacteria, which are also in a physiological state that renders them more resistant. Molecular mechanisms that take part in the biofilm progression, how they are regulated by environmental signals and the genes involved in these processes have been extensively studied, both in vitro and in vivo. One of the main findings is the central role of the second messenger c-di-GMP. High levels of c-di-GMP induce cellular processes that result in the change from a swimming to a sessile phenotype that forms biofilm. One of the signals that induce the biofilm dispersion, the nitric oxide, activates proteins that degrade c-di-GMP, which result in a return to the planktonic phenotype. A preliminary study from our laboratory has shown that the ECF à PA14_46810 physically interacts with the diguanylate cyclase DgcP. In this project, we propose the study of the protein PA14_46810 focusing on its putative role in biofilm progression. The interaction between PA14_46810 with DgcP will also be analyzed in order to elucidate the role of the à factor on the levels of c-di-GMP. Given the known role o c-di-GMP on the biofilm progression, the interaction between these two proteins might have a significant biological effect which elucidation may contribute to the design of new strategies to combat biofilms, contributing to the resolution of infections caused by P. aeruginosa and other bacterial pathogens. (AU)