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Evaluation of the capsule role in the pathogenesis of Legionella longbeachae infections in mice

Grant number: 22/16844-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2023
Effective date (End): December 31, 2024
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Danielle Pini Alves Mascarenhas
Grantee:Pedro Henrique Medeiros Câmara
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens, AP.TEM

Abstract

Bacteria of the genus Legionella are intracellular, Gram-negative organisms that cause a severe form of pneumonia known as Legionnaires' Disease. Among the best-known species, we have Legionella pneumophila, well described in the literature, and Legionella longbeachae, still little studied, but responsible for most outbreaks of this disease. The transmission of these pathogens occurs through the inhalation of contaminated aerosols that reach the host's airways and allow the bacteria to be phagocytosed by alveolar macrophages and begin to replicate. It is already well established that in C57BL/6 mice, the L. pneumophila species has its replication controlled, mainly through the Naip5/NLRC4 inflammasome pathway. Mice infected with L. longbeachae, on the other hand, present high mortality, as well as high bacterial replication, highlighting the significant difference in infections between these two species of bacteria. Previous studies have also shown that L. longbeachae has virulence factors that differ from other species of the genus. Among them, the presence of a capsule was observed, a well-known virulence factor for other species, but unprecedented for the genus Legionella and still scarce in studies regarding its contribution to the pathogenesis of Legionnaires' disease. Based on these data, this project aims to investigate whether the difference in pathogenicity between L. pneumophila and L. longbeachae is due to the presence of a capsule in the latter. We believe that this work is essential for understanding this disease, as well as opening up possibilities for possible therapeutic targets.

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