Comparative genomics of bacterial toxins associated with type IV secretion systems

• Grant number: 16/09047-8
• Support type: Regular Research Grants
• Duration: September 01, 2017 - August 31, 2019
• Field of knowledge: Biological Sciences - Biology
• Principal researcher: Robson Francisco de Souza
• Grantee: Robson Francisco de Souza
• Home 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

(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; 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)