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

Anand, Amitesh and Verma, Priyanka and Singh, Anil Kumar and Kaushik, Sandeep and Pandey, Rajesh and Shi, Ce and Kaur, Harneet and Chawla, Manbeena and Elechalawar, Chandra Kumar and Kumar, Dhirendra and Yang, Yong and Bhavesh, Neel S and Banerjee, Rajkumar and Dash, Debasis and Singh, Amit and Natarajan, Vivek T and Ojha, Anil K and Aldrich, Courtney C and Gokhale, Rajesh S (2015) Polyketide Quinones Are Alternate Intermediate Electron Carriers during Mycobacterial Respiration in Oxygen-Deficient Niches. In: MOLECULAR CELL, 60 (4). pp. 637-650. (In Press)

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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 oxygenrich 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.

Item Type:	Journal Article
Publication:	MOLECULAR CELL
Publisher:	CELL PRESS
Additional Information:	Copy right for this article belongs to the CELL PRESS, 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	18 Feb 2016 06:48
Last Modified:	18 Feb 2016 06:48
URI:	http://eprints.iisc.ac.in/id/eprint/53255

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