Whole-transcriptome analysis of Mycobacterium tuberculosis and macrophages infected with M. tuberculosis against compounds of thiosemicarbazone and hydrazide/hydrazone classes

• Grant number: 11/20527-8
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2012
• End date: April 30, 2014
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Mario Hiroyuki Hirata
• Grantee: Mario Hiroyuki Hirata
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Clarice Queico Fujimura Leite ; Rosario Dominguez Crespo Hirata

Abstract

Tuberculosis (TB) is responsible for the annual death of two to three million people in the world, and since 1960, no new specific drug was discovered against M. tuberculosis. For the viability of this new drug, it should shorten the treatment time to be active against strains resistant and/or MDR and be active against latent bacilli. In this sense, compounds of thiosemicarbazones and hydrazide/hydrazone classes are presented as potential anti-TB agents, having completed chemical assays testing of synthesis and characterization and biological assays, with an excellent activity against the standard strain M. tuberculosis H37Rv. The current proposal aims to determine the action mechanism of these compounds by analyzing the whole-transcriptome of M. tuberculosis and also to evaluate the interaction and persistence of bacilli in the macrophage, by analyzing the transcriptome of infected macrophages. The antimicrobial action of these compounds will be proven against a panel of M. tuberculosis resistant to the drugs isoniazid, rifampicin, streptomycin and ethambutol, as well as in vitro cultures of macrophages infected with the same clinical isolates. As expected results, the proposal aims to identify the genes involved in metabolic pathway in response to these compounds, in order to gain a better understanding of bacilli-macrophage interaction and attempt to propose a new anti-TB drug. (AU)