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In vivo biosynthesis of terpene nucleosides provides unique chemical markers of Mycobacterium tuberculosis infection

Young, David C. and Layre, Emilie and Pan, Shih-Jung and Tapley, Asa and Adamson, John and Seshadri, Chetan and Wu, Zhongtao and Buter, Jeffrey and Minnaard, Adriaan J. and Coscolla, Mireia and Gagneux, Sebastien and Copin, Richard and Ernst, Joel D. and Bishai, William R. and Snider, Barry B. and Moody, D. Branch. (2015) In vivo biosynthesis of terpene nucleosides provides unique chemical markers of Mycobacterium tuberculosis infection. Chemistry & biology, Vol. 22, H. 4. pp. 516-526.

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Official URL: http://edoc.unibas.ch/dok/A6381876

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Abstract

Although small molecules shed from pathogens are widely used to diagnose infection, such tests have not been widely implemented for tuberculosis. Here we show that the recently identified compound, 1-tuberculosinyladenosine (1-TbAd), accumulates to comprise <1% of all Mycobacterium tuberculosis lipid. In vitro and in vivo, two isomers of TbAd were detected that might serve as infection markers. Using mass spectrometry and nuclear magnetic resonance, we established the structure of the previously unknown molecule, N(6)-tuberculosinyladenosine (N(6)-TbAd). Its biosynthesis involves enzymatic production of 1-TbAd by Rv3378c followed by conversion to N(6)-TbAd via the Dimroth rearrangement. Intact biosynthetic genes are observed only within M. tuberculosis complex bacteria, and TbAd was not detected among other medically important pathogens, environmental bacteria, and vaccine strains. With no substantially similar known molecules in nature, the discovery and in vivo detection of two abundant terpene nucleosides support their development as specific diagnostic markers of tuberculosis.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier Science
ISSN:1074-5521
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Jun 2015 08:52
Deposited On:05 Jun 2015 08:52

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