Martin Audrey, Daniel Jaiyanth
Department of Biology, Indiana University-Purdue University Fort Wayne, Fort Wayne, IN 46805, United States of America.
Department of Biology, Indiana University-Purdue University Fort Wayne, Fort Wayne, IN 46805, United States of America.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):667-672. doi: 10.1016/j.bbrc.2018.01.115.
Mycobacterium tuberculosis (Mtb), which causes tuberculosis, is capable of accumulating triacylglycerol (TAG) by utilizing fatty acids from host cells. ATP-binding cassette (ABC) transporters are involved in transport processes in all organisms. Among the classical ABC transporters in Mtb none have been implicated in fatty acid import. Since the transport of fatty acids from the host cell is important for dormancy-associated TAG synthesis in the pathogen, mycobacterial ABC transporter(s) could potentially be involved in this process. Based on sequence identities with a bacterial ABC transporter that mediates fatty acid import for TAG synthesis, we identified Rv1272c, a hitherto uncharacterized ABC-transporter in Mtb that also shows sequence identities with a plant ABC transporter involved in fatty acid transport. We expressed Rv1272c in E. coli and show that it enhances the import of radiolabeled fatty acids. We also show that Rv1272c causes a significant increase in the metabolic incorporation of radiolabeled long-chain fatty acids into cardiolipin, a tetra-acylated phospholipid, and phosphatidylglycerol in E. coli. This is the first report on the function of Rv1272c showing that it displays a long-chain fatty acid transport function.
导致结核病的结核分枝杆菌(Mtb)能够利用宿主细胞中的脂肪酸积累三酰甘油(TAG)。ATP结合盒(ABC)转运蛋白参与所有生物体的运输过程。在Mtb的经典ABC转运蛋白中,没有一个与脂肪酸导入有关。由于宿主细胞中脂肪酸的运输对于病原体中与休眠相关的TAG合成很重要,分枝杆菌ABC转运蛋白可能参与了这一过程。基于与介导脂肪酸导入以合成TAG的细菌ABC转运蛋白的序列同一性,我们鉴定出Rv1272c,它是Mtb中一个迄今未被表征的ABC转运蛋白,并且与参与脂肪酸运输的植物ABC转运蛋白也具有序列同一性。我们在大肠杆菌中表达了Rv1272c,并表明它增强了放射性标记脂肪酸的导入。我们还表明,Rv1272c导致放射性标记的长链脂肪酸在大肠杆菌中代谢掺入心磷脂(一种四酰化磷脂)和磷脂酰甘油的量显著增加。这是关于Rv1272c功能的首次报道,表明它具有长链脂肪酸运输功能。