Structural and functional characterization of the interaction between FleQ and FleN, transcription factors involved in the regulation of flagella biosynthesis in Pseudomonas aeruginosa

• Grant number: 17/11638-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2017
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Marcos Vicente de Albuquerque Salles Navarro
• Grantee: Wesley Cardoso Generoso
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Several bacterial species are able to form biofilms, which are cell aggregates attached to biotic or abiotic superficies. These biofilms are composed by cells shrouded by a matrix that hinders the diffusion of antibiotics and antibodies, and are therefore important for the resistance of pathogens. Furthermore, some cells can detach the biofilm under suitable conditions and start new sessile communities, which trigger chronical intermittent infections. Pseudomonas aeruginosa is an important opportunist pathogen, which is resistant to several known antibiotics. Moreover, P. aeruginosa is also able to form biofilms and thereby the treatment of infected patients is severer. FleQ is the main protein that switches the bacterial lifestyle between the free, mobile phase and the biofilm. This mechanism is dependent of the interaction of FleQ with c-di-GMP. The transcription of genes related with the biofilm formation is derepressed if FleQ is complexed with c-di-GMP, whereas, without c-di-GMP, FleQ activates the transcription of genes involved in the formation of the flagellum, through factor Ã54. In this manner, FleQ acts as a bacterial enhancer binding protein and its regulation occur via interaction with FleN. It is known that the deletion of fleN produces multiflagellated mutants, while its overexpression inhibits flagellum formation. Therefore, this project aims to research the molecular mechanisms of FleQ regulation by FleN and, consequently, to understand the feedback system that regulates the formation of the single flagellum in P. aeruginosa.