Polyketide Quinones Are Alternate Intermediate Electron Carriers during Mycobacterial Respiration in Oxygen-Deficient Niches

Amitesh Anand, Priyanka Verma, Anil Kumar Singh, Sandeep Kaushik, Rajesh Pandey, Ce Shi, Harneet Kaur, Manbeena Chawla, Chandra Kumar Elechalawar, Dhirendra Kumar, Yong Yang, Neel S. Bhavesh, Rajkumar Banerjee, Debasis Dash, Amit Singh, Vivek T. Natarajan, Anil K. Ojha, Courtney C. Aldrich, Rajesh S. Gokhale

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Mycobacterium tuberculosis (Mtb) adaptation to hypoxia is considered crucial to its prolonged latent persistence in humans. Mtb lesions are known to contain physiologically heterogeneous microenvironments that bring about differential responses from bacteria. Here we exploit metabolic variability within biofilm cells to identify alternate respiratory polyketide quinones (PkQs) from both Mycobacterium smegmatis (Msmeg) and Mtb. PkQs are specifically expressed in biofilms and other oxygen-deficient niches to maintain cellular bioenergetics. Under such conditions, these metabolites function as mobile electron carriers in the respiratory electron transport chain. In the absence of PkQs, mycobacteria escape from the hypoxic core of biofilms and prefer oxygen-rich conditions. Unlike the ubiquitous isoprenoid pathway for the biosynthesis of respiratory quinones, PkQs are produced by type III polyketide synthases using fatty acyl-CoA precursors. The biosynthetic pathway is conserved in several other bacterial genomes, and our study reveals a redox-balancing chemicocellular process in microbial physiology.

Original languageEnglish
Pages (from-to)637-650
Number of pages14
JournalMolecular cell
Volume60
Issue number4
DOIs
StatePublished - Nov 19 2015

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