Transcriptome analysis of Mycobacterium tuberculosis strains infecting giant multinucleated cells, activated with vitamin A and D, using a next generation sequencer

• Grant number: 11/08625-4
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2011
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• 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: Elsa Masae Mamizuka ; Raphael Bessa Parmigiani ; Rosario Dominguez Crespo Hirata

Abstract

Tuberculosis treatment is cumbersome and requires at least six months for completion. There are a reduced number of drugs available for the treatment and the acquisition of resistance became a world public health problem. The ability to survive in harsh environments, including macrophages, for long periods of time has been described as one of the most import ability of Mycobacterium tuberculosis (MTB) to infect the mankind. Although highly important, the gene expression of MTB during this persistent phase is still to be completely understood. Yet, the role of non-coding RNA in this process is unknown. In this project, we aim to research, In vitro, the whole gene expression profile of MTB inside giant multinucleated macrophages. The possible role of non-coding RNA will also be investigated. Giant multinucleated cells will be infected with MTB for a period of 30 days. Total RNA extraction will be carried out and sequenced on a Solid XL 5500, a next generation sequencing platform. The gene expression profile of M. tuberculosis W-beijijng strain, M. tuberculosis H37Rv, a Brazilian multirresistant clinical isolate will be compared. It is expected that the results obtained provide new insights into the ability of MTB to survive in difficult environments and novel molecular targets for tuberculosis treatment. (AU)