Yingying Cui,Guanghui Dang,Hui Wang,Yiyi Tang,Mingyue Lv,Xinxin Zang,Zhuming Cai,Ziyin Cui,Jun Cao,Siguo Liu,Ningning Song

DNA Cell Biol.2022 Nov 17.doi: 10.1089/dna.2022.0282. Online ahead of print.

Abstract

l-Arginine serves as a carbon and nitrogen source and is critical for  Mycobacterium tuberculosis  (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the  argCJBDFGH  gene cluster. In this study, we report that the dormancy regulator DosR is a novel arginine regulator binding to the promoter region of  argC  ( rv1652 ), which regulates arginine synthesis. Phosphorylation modification promoted DosR binding to a region upstream of the promoter. Cofactors, including arginine and metal ions, had an inhibitory effect on this association. Furthermore, DosR regulatory function relies on the interaction of the 167, 181, 182, and 197 amino acid residues with an inverse complementary sequence. Arginine also binds to DosR and directly affects its DNA-binding ability. Together, the results demonstrate that DosR acts as a novel transcriptional regulator of arginine synthesis in  Mycobacterium bovis  bacille Calmette-Guerin.

Keywords: ChIP; DosR; Mycobacterium bovis BCG; arginine synthesis; transcriptional regulation.