Nazarova Evgeniya V, Montague Christine R, La Thuy, Wilburn Kaley M, Sukumar Neelima, Lee Wonsik, Caldwell Shannon, Russell David G, VanderVen Brian C
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, United States.
Elife. 2017 Jun 27;6:e26969. doi: 10.7554/eLife.26969.
Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability. We also demonstrate that Mce1 functions as a fatty acid transporter in Mtb and determine that facilitating cholesterol and fatty acid import via Rv3723/LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key function for Rv3723/LucA in in coordinating thetransport of both these substrates.
致病细菌已经进化出高度专业化的系统,以便从宿主中获取必需的营养物质。结核分枝杆菌(Mtb)摄取脂质(胆固醇和脂肪酸)以维持在哺乳动物体内的感染,但此前尚不清楚Mtb中负责脂肪酸导入的机制和蛋白质。在这里,我们鉴定并确定了此前未被表征的蛋白质Rv3723/LucA,其功能是整合Mtb中胆固醇和脂肪酸的摄取。Rv3723/LucA与Mce1和Mce4复合物的亚基相互作用,通过维持其稳定性来协调这些营养转运蛋白的活性。我们还证明Mce1在Mtb中作为脂肪酸转运蛋白发挥作用,并确定通过Rv3723/LucA促进胆固醇和脂肪酸的导入是体内细菌完全致病所必需的。这些数据表明,在Mtb中脂肪酸和胆固醇的同化作用紧密相连,并揭示了Rv3723/LucA在协调这两种底物转运方面的关键作用。