Farrow Mary F, Rubin Eric J
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
J Bacteriol. 2008 Mar;190(5):1783-91. doi: 10.1128/JB.01046-07. Epub 2007 Dec 21.
The lprG-Rv1410c operon is critical for the survival of Mycobacterium tuberculosis during infection, but very little is known about the functions of its proteins. LprG is a lipoprotein, and Rv1410c encodes the major facilitator superfamily small molecule transporter P55. P55 likely exports small molecules outside of the bacterial cell, but the function of LprG is unclear. A deletion of the homologous operon in Mycobacterium smegmatis is more susceptible to ethidium bromide, and drug resistance is restored by the intact operon from M. tuberculosis. The multidrug resistance pump inhibitor reserpine inhibits resistance to ethidium bromide in both wild-type M. smegmatis and the complemented mutant, suggesting that P55-mediated transport is responsible for drug resistance and that ethidium bromide is a novel substrate for P55. In addition to hypersensitivity to ethidium bromide, cells that lack the lprG-Rv1410c operon display abnormal colony morphology and are defective for sliding motility, properties that suggest an alteration of cell wall composition. Strikingly, both ethidium bromide transport and normal cell surface properties require functional P55 and LprG, as neither alone is sufficient to restore function to the deletion mutant. Thus, P55 requires the cell surface lipoprotein for normal function.
lprG-Rv1410c操纵子对于结核分枝杆菌在感染期间的存活至关重要，但其蛋白质的功能却鲜为人知。LprG是一种脂蛋白，Rv1410c编码主要易化子超家族小分子转运蛋白P55。P55可能将小分子转运到细菌细胞外，但LprG的功能尚不清楚。耻垢分枝杆菌中同源操纵子的缺失使其对溴化乙锭更敏感，而来自结核分枝杆菌的完整操纵子可恢复其耐药性。多药耐药泵抑制剂利血平可抑制野生型耻垢分枝杆菌和互补突变体对溴化乙锭的耐药性，这表明P55介导的转运与耐药性有关，且溴化乙锭是P55的一种新底物。除了对溴化乙锭高度敏感外，缺乏lprG-Rv1410c操纵子的细胞还表现出异常的菌落形态，且滑动运动存在缺陷，这些特性表明细胞壁组成发生了改变。引人注目的是，溴化乙锭转运和正常细胞表面特性都需要功能性的P55和LprG，因为单独任何一个都不足以恢复缺失突变体的功能。因此，P55需要细胞表面脂蛋白才能正常发挥功能。
