Bringing Down the Wall of the Mycobacterium tuberculosis Fortress: Old and New Inhibitors of Mycolic Acid Biosynthesis
Hector R.. Morbidoni.
Mycobacterium tuberculosis (the causative agent of tuberculosis), is a stealthy pathogen with a great ability to successfully infect humans and a strong will to stay in the host as long as possible. As much as one admires it as a microbiological entity, M. tuberculosis is also a killer at large responsible for an annual death toll of more than two million people worldwide. Treatment of tuberculosis is a lengthy process that requires multiple drugs for at least six months and although a worldwide health policies established by World Health Organization (WHO) helped reducing the rate of treatment failure, the appearance of novel forms of drug- resistant M. tuberculosis has become a major issue during the last years. The advances in the knowledge of the genetics of this pathogen have allowed for a better understanding of its physiology which in turn helped unveiling the mechanisms of drug action and the ensuing mechanisms of resistance. Surprisingly, it was found that most of the specific anti-tubercular drugs target the synthesis of mycolic acids, long chain fatty acids that are essential components of the cell wall structure. This review highlights the studies on anti-tubercular agents that abrogate the synthesis of mycolic acids with special emphasis on molecules that might be added to the therapeutic weaponry to treat tuberculosis.
Keywords: Tuberculosis, mycolic acid biosynthesis, enoyl-ACP reductase, isoniazid, ethionamide, isoxyl, thiacetazone
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