Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth

作者：L.N. Glass, Ganduri Swapna, Sivagami Sundaram Chavadi, JoAnn M. Tufariello, Kaixia Mi, Joshua E. Drumm, TuKiet T. Lam, Guofeng Zhu, Chenyang Zhan, Catherine Vilchèze, Jesús Arcos, Yong Chen, Lijun Bi, Simren Mehta, Steven A. Porcelli, S.C. Almo, Syun‐Ru Yeh, William R. Jacobs, Jordi B. Torrelles, John Chan · 发表于：PLoS Pathogens · 年份：2017 · DOI：10.1371/journal.ppat.1006515 · 被引用次数：62 · 研究领域：Peptidase Inhibition and Analysis、Tuberculosis Research and Epidemiology、Bacterial Genetics and Biotechnology

We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence. Here, yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA domains are signaling protein modules that mediate protein-protein interactions to modulate a wide variety of biological processes via binding to conserved phosphorylated threonine (pT)-containing oligopeptides of the interactors. Biochemical, immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT and specifically identified threonine 237 as a phosphorylated residue. Relative to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction with the Rv1747 FHA I domain and diminished growth-regulatory capacity. Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant (ΔRv2623) displays enhanced expression of phosphatidyl-myo-inositol mannosides (PIMs), while the ΔRv1747 mutant expresses decreased levels of PIMs. Animal studies have previously shown that ΔRv2623 is hypervirulent, while ΔRv1747 is growth-attenuated. Collectively, these data have provided evidence that Rv2623 interacts with Rv17...