Cloning and antibacterial activity of novel Salmonella T6SS effectors

• Grant number: 20/15389-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2021
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Ethel Bayer Santos
• Grantee: Gustavo Chagas Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/02178-2 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells, AP.JP

Abstract

Bacteria use a wide range of toxic proteins to gain competitive advantages over other species in the vicinity. Bacteria encode protein secretion systems that secrete these toxins into the extracellular medium or into target cells. The type VI secretion system (T6SS) has a structure homologous to the contractile tail of bacteriophages, and it is anchored in the internal membrane of Gram-negatives. T6SS can be used to inject toxic proteins (effectors) into prokaryotes or eukaryotes. Bacteria of the Salmonella genus use the T6SS to compete with species of the microbiota and for host colonization. Bioinformatics analyzes in 10k Salmonella genomes (10KSG consortium) carried out by our group allowed us to detect a large number of putative T6SS effectors. The aim of this project is to clone some of the most promising candidates and test their antibacterial activity. The identification and characterization of new Salmonella effectors has economic and clinical implications given the diversity of vertebrates susceptible to these bacteria. Due to the vast distribution of T6SS in Gram-negatives (25%), the knowledge generated with this project can be applied to other species. In addition, the characterization of new antibacterials has the potential to develop new therapeutic targets to combat antibiotic resistance.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HESPANHOL, JULIA TAKUNO; SANCHEZ-LIMACHE, DANIEL ENRIQUE; NICASTRO, GIANLUCCA GONCALVES; MEAD, LIAM; LLONTOP, EDGAR ENRIQUE; CHAGAS-SANTOS, GUSTAVO; FARAH, CHUCK SHAKER; DE SOUZA, ROBSON FRANCISCO; GALHARDO, RODRIGO DA SILVA; LOVERING, ANDREW L.; et al. Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases. eLIFE, v. 11, p. 26-pg., 2022-10-13. (17/17303-7, 19/12234-2, 21/03400-6, 16/09047-8, 20/15389-4, 18/25316-4, 18/04553-8, 17/02178-2, 19/22715-8)