Structure-Aware Mycobacterium tuberculosis Functional Annotation Uncloaks Resistance, Metabolic, and Virulence Genes
Samuel J. Modlin, Afif Elghraoui, Deepika Gunasekaran, Alyssa M. Zlotnicki, Nicholas Dillon, Nermeeta Dhillon, Norman Kuo, Cassidy Robinhold, Carmela K. Chan, Anthony D. Baughn, Faramarz Valafar
Abstract
functional screens added functional information to dozens of clinically pertinent proteins described as having unknown function. Integrating the annotations with a prospective functional screen identified new mutants resistant to a first-line TB drug, supporting an emerging hypothesis for its mode of action. These improvements in functional interpretation of clinically informative studies underscore the translational value of this functional knowledge. Structure-derived annotations identify hundreds of high-confidence candidates for mechanisms of antibiotic resistance, virulence factors, and basic metabolism and other functions key in clinical and basic tuberculosis research. More broadly, they provide a systematic framework for improving prokaryotic reference annotations.