Comparative genomics of bacterial toxins associated with type IV secretion systems

• Grant number: 16/09047-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2017
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Robson Francisco de Souza
• Grantee: Robson Francisco de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Bacteria are subject to many different varieties of biological conflict, like competition between different lineages of the same species, competition between different species or interactions between pathogenic bacteria and their hosts. When engaging in such conflicts, bacteria often deploy proteinaceous toxins that contain effector domains belonging to many different families and based on a diverse array of molecular mechanisms. Such toxins are also associated with an equally diverse repertoire of antitoxins whose function is to neutralize the corresponding toxins, avoiding death of the producing cell. As observed in other instances of biological conflict, bacterial toxins are characterized by the rapid gene evolution, a consequence of the continuous evolution of defense strategies by adversaries. The most visible effect of these arm's races is the high rate of de novo appearance of new toxin domains and of novel combinations of toxic effectors and secretion or processing domains. These phenomena make bacterial toxins interesting targets for the study of the evolutionary process involved in their origin and diversification. In this project, our aim is to apply comparative genomics' methods to study a class of toxins that act as Tfes ("Type four secretion system associated effectors"). We will: (i) search and classify novel effector domains in toxins and novel antitoxins associated with the type IV secretion systems, (ii) investigate the evolutionary history and processes affecting these domain families, (iii) apply genomic context analysis to generate hypothesis on the biochemical mode of action of toxins and antitoxins and (iv) experimentally validate predicted molecular functions and interactions for a subset of the identified toxins. In summary, our analyses will reveal new toxins and antitoxins, with potential for the discovery of new biochemical mechanisms and modes of action, and shed more light on the nature of evolutionary processes influencing competition among different species of bacteria. (AU)

Scientific publications

(7)

(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)

DE SOUZA, ANACLETO SILVA; AMORIM, VITOR MARTINS DE FREITAS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FELIPE R. C.; DOS SANTOS, FILIPE F.; DE SOUZA, ROBSON FRANCISCO; JUVENAL, GUILHERME DE ARAUJO; HUANG, YIHUA; GE, PINGJU; JIANG, YINAN; et al. Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2. ACS OMEGA, v. 7, n. 35, p. 10-pg., 2022-08-24. (20/06091-1, 17/18246-7, 17/19541-2, 20/04680-0, 19/00195-2, 16/09047-8, 18/15579-8, 18/07366-4, 20/14158-9)

DE SOUZA, ANACLETO SILVA; DE FREITAS AMORIM, VITOR MARTINS; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v. N/A, p. 18-pg., 2022-10-29. (20/04680-0, 21/00070-5, 19/00195-2, 16/09047-8)

DE SOUZA, ANACLETO SILVA; DE FREITAS AMORIM, VITOR MARTINS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FILIPE F.; ULRICH, HENNING; GALANTE, PEDRO A. F.; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Perspective for Emerging More Transmissible and Vaccine-Resistant Strains. Viruses-Basel, v. 14, n. 4, p. 21-pg., 2022-04-01. (18/07366-4, 20/06091-1, 19/00195-2, 16/09047-8, 20/14158-9, 20/04680-0, 17/18246-7, 17/19541-2, 18/15579-8)

DE SOUZA, ANACLETO SILVA; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Quantitative structure-activity relationships, molecular docking and molecular dynamics simulations reveal drug repurposing candidates as potent SARS-CoV-2 main protease inhibitors. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, JUL 2021. (20/04680-0, 19/00195-2, 16/09047-8)

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)

DE SOUZA, ANACLETO SILVA; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Quantitative structure-activity relationships, molecular docking and molecular dynamics simulations reveal drug repurposing candidates as potent SARS-CoV-2 main protease inhibitors. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v. 40, n. 21, p. 18-pg., 2022-01-01. (19/00195-2, 16/09047-8, 20/04680-0)

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)