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J Bacteriol. 2009 Nov;191(21):6584-91. doi: 10.1128/JB.00488-09. Epub 2009 Aug 28.

Mycobacterium tuberculosis is able to accumulate and utilize cholesterol.

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  • 1Institute for Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.

Abstract

It is expected that the obligatory human pathogen Mycobacterium tuberculosis must adapt metabolically to the various nutrients available during its cycle of infection, persistence, and reactivation. Cholesterol, which is an important part of the mammalian cytoplasmic membrane, is a potential energy source. Here, we show that M. tuberculosis grown in medium containing a carbon source other than cholesterol is able to accumulate cholesterol in the free-lipid zone of its cell wall. This cholesterol accumulation decreases the permeability of the cell wall for the primary antituberculosis drug, rifampin, and partially masks the mycobacterial surface antigens. Furthermore, M. tuberculosis was able to grow on mineral medium supplemented with cholesterol as the sole carbon source. Targeted disruption of the Rv3537 (kstD) gene inhibited growth due to inactivation of the cholesterol degradation pathway, as evidenced by accumulation of the intermediate, 9-hydroxy-4-androstene-3,17-dione. Our findings that M. tuberculosis is able to accumulate cholesterol in the presence of alternative nutrients and use it when cholesterol is the sole carbon source in vitro may facilitate future studies into the pathophysiology of this important deadly pathogen.

PMID:
19717592
PMCID:
PMC2795286
DOI:
10.1128/JB.00488-09
[PubMed - indexed for MEDLINE]
Free PMC Article
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