title: Radiation-sensitive gene A (RadA) targets DisA, DNA integrity scanning protein A, to negatively affect cyclic Di-AMP synthesis activity in Mycobacterium smegmatis.
abstract: Cyclic di-AMP has been recognized as a ubiquitous second messenger involved in the regulation of bacterial signal transduction. However, little is known about the control of its synthesis and its physiological role in bacteria. In this study, we report a novel mechanism of control of c-di-AMP synthesis and its effects on bacterial growth in Mycobacterium smegmatis. We identified a DisA homolog in M. smegmatis, MsDisA, as an enzyme involved in c-di-AMP synthesis. Furthermore, MsRadA, a RadA homolog in M. smegmatis was found to act as an antagonist of the MsDisA protein. MsRadA can physically interact with MsDisA and inhibit the c-di-AMP synthesis activity of MsDisA. Overexpression of MsdisA in M. smegmatis led to cell expansion and bacterial aggregation as well as loss of motility. However, co-expression of MsradA and MsdisA rescued these abnormal phenotypes. Furthermore, we show that the interaction between RadA and DisA and its role in inhibiting c-di-AMP synthesis may be conserved in bacteria. Our findings enhance our understanding of the control of c-di-AMP synthesis and its physiological roles in bacteria.
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zheng-Guo
authors.initials: ZG
authors.lastname: He
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000096:biosynthesis*; D008855:Microscopy, Electron, Scanning; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; C100901:RadA protein, bacteria; C528998:cyclic diadenosine phosphate
keywords: Bacterial Genetics; Bacterial Signal Transduction; Cell Growth; Cell Motility; Cyclic di-AMP; Metabolic Regulation; Multifunctional Enzymes; Mycobacteria