Mycobacterium tuberculosis Is Able To Accumulate and Utilize Cholesterol
Mycobacterium tuberculosis Is Able To Accumulate and Utilize Cholesterol
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DOI：
10.1128/jb.00488-09
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发表时间：
2009-11-01
影响因子：
3.2
通讯作者：
Dziadek, Jaroslaw
中科院分区：
文献类型：
--
作者：
Brzostek, Anna;Pawelczyk, Jakub;Dziadek, Jaroslaw
预期专性人类病原体结核分枝杆菌在其感染、持续和再活化的周期期间必须代谢适应可获得的各种营养物。胆固醇是哺乳动物细胞膜的重要组成部分，是一种潜在的能量来源。在这里，我们表明，M。在含有除胆固醇以外的碳源的培养基中生长的结核菌能够在其细胞壁的游离脂质区中积累胆固醇。这种胆固醇的积累降低了细胞壁对主要抗结核药物利福平的渗透性，并部分掩盖了分枝杆菌表面抗原。此外，M。结核菌能够在补充有胆固醇作为唯一碳源的矿物培养基上生长。靶向破坏Rv 3537（kstD）基因抑制生长，由于胆固醇降解途径的失活，如中间体9-羟基-4-雄烯-3，17-二酮的积累所证明的。我们的研究结果表明，M.结核病能够在替代营养物存在下积累胆固醇，并在胆固醇是体外唯一碳源时利用胆固醇，这可能有助于今后对这种重要致命病原体的病理生理学进行研究。
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.