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LsfA in inflammation: roles of an antioxidant protein in pro-inflammatory and pro-resolving lipid mediators

Grant number: 21/11077-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): March 01, 2022
Effective date (End): June 30, 2022
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Luis Eduardo Soares Netto
Grantee:Rogério Luis Aleixo Silva
Supervisor: Jesmond Dalli
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Queen Mary University of London, England  
Associated to the scholarship:20/00845-4 - Unraveling the biological role of LsfA, a 1-Cys Prx involved in the P. aeruginosa virulence, BP.DR

Abstract

Pseudomonas aeruginosa is a ubiquitous and opportunistic pathogen that is exposed to an oxidative burst among other stresses during host invasion. To overcome this challenge, bacteria use a set of antioxidant proteins, including LsfA, a peroxiredoxin involved with the bacterial virulence that is capable to reduce H2O2 and other hydroperoxides at extremely fast rates. Thereby, LsfA protects bacteria from oxidants derived from NOX-2, interfering in redox processes at the host pathogen interface. Notably, mice infected with bacteria devoid of LsfA presented activation of NF-º² pathway, increased TNF-± production and increased neutrophil recruitment. Of note, peroxiredoxins can also reduce fatty acid hydroperoxides generated by lipoxygenases (5-LOX, LOX-12) and cyclooxygenases (COX-2), whose genes are regulated by NF-º². Lipid mediators generated by lipoxygenases and cyclooxygenases are well known to regulate pro-inflammatory and resolution processes, as lipoxins and resolvins. Therefore, our objective here is to understand how LsfA interferes with the production of oxidants and lipid mediators by the host. We intend to verify if hydroperoxides of lipid mediator pathways are reduced by LsfA in enzymatic systems. Also, we intend to characterize the kinetics of this reaction. Furthermore, we will co-incubate differentiated macrophages (M1 or M2) with P. aeruginosa strains (WT or ”lsfA) and quantify the production of lipid mediators by LC-MS-MS to identify which pathways might be affected by LsfA. (AU)

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