Miguel Mitchell's blog

30 Mar

XDR Tuberculosis: The New Threat

Published by Miguel Mitchell

XDR tuberculosis is resistant to the first-line anti-TB drugs and at least 3 out of 6 of the second line anti-TB drugs. It has an estimated 85% mortality rate. Clearly we're talking about a monster.

30 Mar

My Antitubercular Research: Pitfalls and Recent Discoveries

Published by Miguel Mitchell

I am happy to report that my group in collaboration with Scott Franzblau from the Institute for Tuberculosis Research at U. Illinois-Chicago has published our anti-TB work (see attachment). We explored the quaternized promazine derivatives as antitubercular agents, and found that the most potent thus far are 4- and 3-chlorophenyl derivatives of triflupromazine, both nontoxic in vitro against Vero cells. In our unpublished studies, we have also discovered that both of these actives are bacteriocidal against M. tuberculosis and that the 4-chlorobenzyl derivative is as bacteriocidal as rifampin, the most potent clinically prescribed antitubercular drug. So we're quite happy!

14 Aug

Development of Novel Antitubercular Drugs

Published by Miguel Mitchell

 

This is a call for creating a tuberculosis research community.

Background

Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), infects approximately two billion people. The World Health Organization estimates that about two million people die each year from TB due to the lack of and inability to afford proper health care.1 Overcrowding and ill-nourishment of poor people living in large cities leads to a high incidence of the disease due to the ease at which the infection can be transferred.2 This contributes to the accelerated speed at which TB spreads in underdeveloped countries. There is also an alarming increase in cases of TB caused by multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), due in part to inadequate drug therapy as a result of incorrectly selected medications or suboptimal drug dosing.3 Thus, there is a need for new drugs targeting enzymes essential to mycobacterial survival.

Research Focus 

My lab is focusing on the inhibition of type II NADH-menaquinone dehydrogenase (ndh-2). By inhibiting ndh-2, the electron transport chain in Mtb becomes blocked and shuts down. Ndh-2 is the only NADH dehydrogenase enzyme expressed in Mtb and is thus vital to its survival.4 Ndh-2 is also found in a number of other bacteria such as Staphylococcus aureus and Enterococcus faecalis but is not expressed in humans.5 Humans rely only on type I NADH dehydrogenase (ndh-1) and thus minimal toxicity in humans is predicted with ndh-2 inhibitors.