Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells

• Grant number: 17/02178-2
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: March 01, 2018
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Ethel Bayer Santos
• Grantee: Ethel Bayer Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Cristiane Rodrigues Guzzo Carvalho ; Robson Francisco de Souza
• Associated scholarship(s): 22/01364-5 - Functional characterization of a new T6SS antibacterial effector of Salmonella enterica, BP.MS; 22/01444-9 - Analysis of the contribution of a new antibacterial T6SS effector of Salmonella enterica serovar Oslo in bacterial competitions, BP.IC; 21/13972-7 - Evaluation of the anti-eukaryotic activity of T6SS effectors from Salmonella spp. using yeast, BP.IC; + associated scholarships 21/09162-0 - Study of the function of different Hcp proteins encoded by Salmonella spp, BP.DD; 21/03400-6 - Development of a universal pipeline for genomic context analysis from different sources of data., BP.TT; 21/02536-1 - Identification of new effectors secreted by the Salmonella T6SS using in silico approaches and functional characterization of a candidate, BP.MS; 20/15389-4 - Cloning and antibacterial activity of novel Salmonella T6SS effectors, BP.IC; 19/27644-1 - Contribution of HCPs to the SPI-6 T6SS-dependent pathogenesis of Salmonella Typhimurium, BP.MS; 19/22715-8 - Function of Salmonella bongori SPI-22 T6SS in bacterial competitions and interactions with phagocytic host cells, BP.MS; 18/25316-4 - Function of SPI-6 T6SS and SPI-19 T6SS of Salmonella during competition with the gut microbiota, BP.IC; 18/13819-1 - Analysis of the activation dynamics of the type 6 secretion system of Salmonella during infection of eukaryotic cells, BP.IC; 18/04553-8 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells, BP.JP - associated scholarships

Abstract

Bacterial secretion systems are versatile structures that secrete proteins and DNA in the extracellular medium or into prokaryotic and eukaryotic cells. Many pathogenic bacteria rely on secretion systems to modulate hosts responses or to defend themselves against competing organisms and predators. The type VI secretion system (T6SS) is present in several animal and plant pathogens. Serotypes of Salmonella enteric comprise facultative intracellular Gram-negative bacteria responsible for causing infections in various vertebrates. Most Salmonella serotypes encode a T6SS in the pathogenicity island SPI-6. However, some serotypes encode a T6SS in SPI-19, and a few examples encode two T6SS (SPI-6 and SPI-19). Deletion of essential T6SS genes reduced bacterial virulence in models of systemic mice and chicken infection, indicating that T6SS plays an important role during infection. However, the function of T6SS during infection of eukaryotic cells was not clarified. In this context, the main goal of this project is to study the function of both Salmonella T6SSs (SPI-6 and SPI-19) during interactions with eukaryotic cells. We will investigate the role of Salmonella T6SS during infection of mammalian cells and free-living amoeba, identifying the proteins secreted, and the molecular mechanisms that regulate the function of these proteins inside eukaryotic cells. There are a few research groups worldwide focused on studying the role of T6SS in the interaction of bacteria with eukaryotic cells and most groups have their attention on bacterial competitions. Since none of these groups are in Brazil, we intend to develop an innovative research field with great international insertion due to its pioneering potential. (AU)

Scientific publications

(10)

(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)

SIBINELLI-SOUSA, STEPHANIE; HESPANHOL, JULIA T.; NICASTRO, GIANLUCCA G.; MATSUYAMA, BRUNO Y.; MESNAGE, STEPHANE; PATEL, ANKUR; DE SOUZA, ROBSON F.; GUZZO, CRISTIANE R.; BAYER-SANTOS, ETHEL. A Family of T6SS Antibacterial Effectors Related to L,D-Transpeptidases Targets the Peptidoglycan. CELL REPORTS, v. 31, n. 12, JUN 23 2020. (18/04553-8, 17/02178-2, 16/09047-8, 19/00195-2, 17/17303-7, 18/25316-4, 16/00458-5, 18/13819-1)

JULIA TAKUNO HESPANHOL; LIOR KARMAN; DANIEL ENRIQUE SANCHEZ-LIMACHE; ETHEL BAYER-SANTOS. Intercepting biological messages: Antibacterial molecules targeting nucleic acids during interbacterial conflicts. GENETICS AND MOLECULAR BIOLOGY, v. 46, n. 1, 2023-03-06. (19/22715-8, 22/01364-5, 22/01444-9, 17/02178-2, 18/04553-8)

BAYER-SANTOS, ETHEL. A journey into Salmonella effectors: Specialized molecules for biological conflicts. CELL HOST & MICROBE, v. 30, n. 4, p. 4-pg., 2022-04-13. (17/02178-2, 18/04553-8)

SIBINELLI-SOUSA, STEPHANIE; HESPANHOL, JULIA TAKUNO; BAYER-SANTOS, ETHEL. Targeting the Achilles' Heel of Bacteria: Different Mechanisms To Break Down the Peptidoglycan Cell Wall during Bacterial Warfare. Journal of Bacteriology, v. 203, n. 7, APR 2021. (18/25316-4, 18/04553-8, 17/02178-2, 19/27644-1)

SIBINELLI-SOUSA, STEPHANIE; DE ARAUJO-SILVA, ANDRE LUIZ; HESPANHOL, JULIA TAKUNO; ETHEL, BAYER-SANTOS. Revisiting the steps of Salmonella gut infection with a focus on antagonistic interbacterial interactions. FEBS Journal, OCT 2021. (18/04553-8, 19/27644-1, 18/25316-4, 17/02178-2, 21/02536-1)

BAYER-SANTOS, ETHEL; CESETI, LUCAS DE MORAES; FARAH, CHUCK SHAKER; ALVAREZ-MARTINEZ, CRISTINA ELISA. Distribution, Function and Regulation of Type 6 Secretion Systems of Xanthomonadales. FRONTIERS IN MICROBIOLOGY, v. 10, JUL 17 2019. (18/04553-8, 17/17303-7, 17/02178-2, 18/01852-4, 17/02318-9)

SGRO, GERMAN G.; OKA, GABRIEL U.; SOUZA, DIORGE P.; CENENS, WILLIAM; BAYER-SANTOS, ETHEL; MATSUYAMA, BRUNO Y.; BUENO, NATALIA F.; DOS SANTOS, THIAGO RODRIGO; ALVAREZ-MARTINEZ, CRISTINA E.; SALINAS, ROBERTO K.; et al. Bacteria-Killing Type IV Secretion Systems. FRONTIERS IN MICROBIOLOGY, v. 10, MAY 21 2019. (17/17303-7, 18/01852-4, 17/02178-2)

BAYER-SANTOS, ETHEL; CENENS, WILLIAM; MATSUYAMA, BRUNO YASUI; OKA, GABRIEL UMAJI; DI SESSA, GIANCARLO; MININEL, IZABEL DEL VALLE; ALVES, TIAGO LUBIANA; FARAH, CHUCK SHAKER. The opportunistic pathogen Stenotrophomonas maltophilia utilizes a type IV secretion system for interbacterial killing. PLOS PATHOGENS, v. 15, n. 9, SEP 2019. (15/25381-2, 17/17303-7, 18/04553-8, 15/18237-2, 17/02178-2, 16/00458-5, 11/07777-5)

COBO, NEIL LORENTE; SIBINELLI-SOUSA, STEPHANIE; BIBOY, JACOB; VOLLMER, WALDEMAR; BAYER-SANTOS, ETHEL; PREHNA, GERD. Molecular characterization of the type VI secretion system effector Tlde1a reveals a structurally altered fold. Journal of Biological Chemistry, v. 298, n. 11, p. 17-pg., 2022-11-02. (17/02178-2, 21/09162-0)