RT Journal Article SR Electronic T1 Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis JF bioRxiv FD Cold Spring Harbor Laboratory SP 121780 DO 10.1101/121780 A1 Evgeniya V. Nazarova A1 Christine R. Montague A1 Thuy La A1 Kaley M. Wilburn A1 Neelima Sukumar A1 Wonsik Lee A1 Shannon Caldwell A1 David G. Russell A1 Brian C. VanderVen YR 2017 UL http://biorxiv.org/content/early/2017/03/29/121780.abstract AB Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts and Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infection in mammals. While the uptake of cholesterol by Mtb is mediated by the Mce4 transporter, the route(s) of uptake of fatty acids remain unknown. Here, we demonstrate that an uncharacterized protein LucA, integrates the assimilation of both cholesterol and fatty acids in Mtb. LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters. We also demonstrate that Mce1 functions as an important fatty acid transporter in Mtb and we determine that the integration of cholesterol and fatty acid transport by 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 role for LucA in coordinating both transport activities.