Caracterização de um novo grupo de efetores pertencente a superfamília NlpC/P60 secretados pelo T6SS de Salmonella spp.

Author(s)

Andre Luiz de Araújo Silva

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2022-11-08

Examining board members

Ethel Bayer Santos; João Marcelo Pereira Alves; Luis Caetano Martha Antunes; Regina Lúcia Baldini

• Advisor: Ethel Bayer Santos; Robson Francisco de Souza

Abstract

Bacteria live in polymicrobial communities and constantly compete for resources. Gram-negative species such as Salmonella spp. encode a type VI protein secretion system (T6SS), which is a contractile apparatus formed by 13 proteins capable of injecting toxic proteins (effectors) into competing bacteria. The genus Salmonella encodes five phylogenetically distinct T6SSs in different pathogenicity islands: Salmonella enterica serotype Typhimurium encodes a T6SS in SPI-6 (Salmonella Pathogenicity Island-6); S. enterica serotype Gallinarum encodes a T6SS in SPI-19; S. arizonae encodes two T6SS on islands SPI-20 and SPI-21; and S. bongori encodes a T6SS in SPI-22. Previous studies have demonstrated the importance of the SPI-6 T6SS for S. Typhimurium and SPI-19 T6SS for S. Gallinarum during infection of vertebrate hosts; however, only four effectors secreted by the T6SSs of Salmonella spp. have been identified so far. The identification of new effectors secreted via T6SSs and the characterization of their mechanisms of action will allow us to understand the contribution of these systems to the pathogenicity of Salmonella, the dynamics of microbial communities and the maintenance of environmental reservoirs of this pathogen, in addition to contributing to the discovery of new antimicrobial mechanisms. Hence, this work aims to characterize a new group of T6SS effectors from Salmonella spp. belonging to the NlpC/P60 superfamily, which was identified using computational approaches during the analysis of 10K genomes of Salmonella (10KSG). Tox241 is a representative member of this group and is toxic when expressed in the periplasm of Escherichia coli. Structural predictions and molecular docking suggest Tox241 is a phospholipase. This work contributes with knowledge about the biochemical weapons used by bacteria in biological conflicts. (AU)

• FAPESP's process: 21/02536-1 - Identification of new effectors secreted by the Salmonella T6SS using in silico approaches and functional characterization of a candidate
• Grantee: Andre Luiz de Araújo Silva
• Support Opportunities: Scholarships in Brazil - Master