El próximo 29 de septiembre a las 12h. la Dra. Inmaculada Pérez Dorado, del instituto de Química-Física Blas Cabrera (CSIC), impartirá un seminario sobre sus últimos avances en el estudio estructural de sistemas de secreción de Mycobacterium y de endolisinas de fagos.
Esta actividad tendrá lugar en la Sala de Conferencias del edificio I+D y está organizada por el Instituto de Investigación en Biocomputación y Sistemas Complejos (BIFI).
Abstract: The Mycobacterium genus contains over 150 recognized species, many of which produce infectious diseases in human such as tuberculosis or leprosy, caused by Mycobacterium tuberculosis (Mtb) and Mycobacterium leprae, respectively. Human tuberculosis is one of the world’s most devastating human ID responsible of ~1.5 million deaths every year; while leprosy is an IDs associated with permanent deformation, disability and stigma, with > 200.000 new cases every year. Our group aims at using structural biology approaches to acquire a deep understanding of biological systems involved in host-pathogen interactions in pathogenic mycobacteria, as well as finding new ways for antimicrobial development. Our work mainly focuses on the study of the ESX5 secretion system and LysA mycobacteriophage-encoded endolysins. The ESX5 secretion system is a complex molecular machine, and key virulence factor essential for the viability of pathogenic mycobacteria, including Mtb. EccC5 is a large ATPase, and pivotal ESX5 component, that provides the secretion driving force via ATP hydrolysis. Our structural studies reveal the lack of ATPase activity proposed for the N-terminal DUF domain of EccC5, which is likely conserved in other ESX systems from mycobacterial and non-mycobacterial species. These results uncover key features of the ESX-dependent secretion mechanism, and it may open new ways for inhibitor development targeting the EccC5-DUF domain. Bacteriophage endolysins are peptidoglycan hydrolases targeting the bacterial surface that, when exogenously applied, can produce a rapid and specific elimination of pathogenic bacteria. In this line, DS6A-LysA and D29-LysA are complex multidomain endolysins with potential antimicrobial application against pathogenic mycobacteria. Our crystallographic studies of DS6A-LysA and D29-LysA catalytic domains uncovers important aspects of the mechanism of cell-wall binding and hydrolysis by these endolysins, knowledge that is key for their potential application as specific antimicrobials.