Proteasomal regulation of hormone signaling in Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) kills about 1.5 million people globally every year, making it the leading causes of death by an infectious agent. The lack of an effective TB vaccine or the development of immunity after TB infection suggests antimicrobial drugs may be our best chance for controlling this disease. The Mycobacterium tuberculosis (Mtb) proteasome is essential to cause lethal infections in animals and, therefore, it is currently being targeted for tuberculosis chemotherapy.My lab is working to understand how a bacterial proteasome allows Mtb to persist in animals by characterizing substrates of the Mtb proteasome. Dozens if not hundreds of proteins that are degraded by the bacterial proteasome must first be post‐translationally modified with the small protein Pup (prokaryotic ubiquitin‐like protein). We reported the identification of a pupylated protein called Lonely Guy (Log) that catalyzes the synthesis of cytokinins, which have previously only been characterized as plant hormones. Log levels are maintained at very low levels in Mtb by the Pup‐proteasome system, suggesting the presence of cytokinins in Mtb requires tight regulation. In my talk, I will discuss exciting new data that addresses the function of Log and cytokinins in Mtb physiology.Support or Funding InformationThis work was supported by NIH grant R01HL092774 awarded to K.H.D. K.H.D. holds an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. Trainees were supported by NIH grant T32 AT007180.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.