ChemMedChem

Cover image for Vol. 11 Issue 23

Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)

Impact Factor: 2.98

ISI Journal Citation Reports © Ranking: 2015: 18/59 (Chemistry Medicinal); 77/255 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

October 08, 2011

VIP: Identification and Characterization of Inhibitors of the Aminoglycoside Resistance Acetyltransferase Eis from Mycobacterium tuberculosis

VIP: Identification and Characterization of Inhibitors of the Aminoglycoside Resistance Acetyltransferase Eis from Mycobacterium tuberculosisKeith D. Green, Wenjing Chen, Sylvie Garneau-Tsodikova*

With a predicted 9.8 million new cases and nearly two million deaths anticipated this year, tuberculosis (TB) is one of the most serious epidemic problems worldwide. The alarming emergence of TB strains resistant to currently available drugs used to treat these infections underscores the need for the discovery of new antibiotics and/or the development of new approaches to combat this deadly disease. Amongst TB drugs, the aminoglycoside antibiotics are used as the last line of defense.

A research team led by Sylvie Garneau-Tsodikova at the University of Michigan (USA) has identified candidate lead compounds that could alleviate some of the drug resistance in TB. Earlier work by the team revealed an unprecedented, complex, and efficient mechanism that M. tuberculosis uses to inactivate aminoglycosides: the multi-acetylation of these antibiotics by the enhanced intracellular survival (Eis) protein.[1] In a new strategy toward overcoming Eis-mediated resistance in TB strains, Garneau-Tsodikova and colleagues next focused on identifying Eis inhibitors which would render aminoglycosides useful again. Using high-throughput screening and biological activity assays, they identified a variety of molecules that abolish Eis activity, thus keeping aminoglycosides active. As reported in ChemMedChem, some of these compounds are actually drugs that are currently approved for the treatment of other diseases (HIV, bacterial infections, and cancer) that may now find new application in the treatment of TB.

[1] W. Chen et al., Proc. Natl. Acad. Sci. USA 2011, 108, 9804–9808.

Received July 1, 2011; published online September 5, 2011, DOI: 10.1002/cmdc.201100332.

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