25º Congresso Brasileiro de Microbiologia
ResumoID:1542-1


Área: Micobacteriologa ( Divisão C )

DECIPHERING THE MODE OF ACTION OF A CARBON SOURCE-DEPENDENT CLASS OF ANTI-TUBERCULOSIS COMPOUNDS

Patricia Carvalho Sequeira (NITD); Mai Ping Tan (NITD); Seow Hwee Ng (NITD); Bee Huat Tan (NITD); Wai Yee Phong (NITD); Jeyaraj Duraiswamy (NITD); Thomas Dick (NITD); Kevin Pethe (NITD)

Resumo

Tuberculosis (TB) is the leading infectious cause of death among the adult population worldwide and the fact that no TB-specific drugs have been discovered in the last 40 years has been a challenge for the scientific community. Understanding the physiology of TB bacilli in vitro and engaging the energy metabolism pathway in chemotherapeutic intervention have been proven to be important approaches towards the development of new drugs against TB. Moreover, one of the major obstacles for eradicating TB by vaccination or chemotherapy is the ability of dormant Mycobacterium tuberculosis to persist within granulomatous lesions. Dormant M. tuberculosis is capable of adapting to an intracellular lifestyle of non-replicating persistence, in which it is phenotypically drug-resistant and responsible for latent TB infection.

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To study the physiology of dormant M. tuberculosis, we have used the anaerobic shift model of latent TB. The effect of different carbon sources on the ability of non-replicating bacteria to persist under hypoxia have been addressed. We have demonstrated that dormant M. tuberculosis cannot persist when excessive amounts of glycerol are present in the media. We have also observed that glycerol toxicity can be reversed when the alternative electron acceptor sodium nitrate is present, suggesting that metabolism of glycerol may interfere with the electron transport chain.

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