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- Title
Cyclic-di- AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in L actococcus lactis.
- Authors
Zhu, Yan; Pham, Thi Huong; Nhiep, Thi Hanh Nguyen; Vu, Ngoc Minh Thu; Marcellin, Esteban; Chakrabortti, Alolika; Wang, Yuanliang; Waanders, Jennifer; Lo, Raquel; Huston, Wilhelmina M.; Bansal, Nidhi; Nielsen, Lars K.; Liang, Zhao‐Xun; Turner, Mark S.
- Abstract
The second messenger cyclic-di-adenosine monophosphate ( c-di-AMP) plays important roles in growth, virulence, cell wall homeostasis, potassium transport and affects resistance to antibiotics, heat and osmotic stress. Most Firmicutes contain only one c-di- AMP synthesizing diadenylate cyclase ( CdaA); however, little is known about signals and effectors controlling CdaA activity and c-di- AMP levels. In this study, a genetic screen was employed to identify components which affect the c-di- AMP level in L actococcus. We characterized suppressor mutations that restored osmoresistance to spontaneous c-di- AMP phosphodiesterase gdp P mutants, which contain high c-di- AMP levels. Loss-of-function and gain-of-function mutations were identified in the cda A and gdp P genes, respectively, which led to lower c-di- AMP levels. A mutation was also identified in the phosphoglucosamine mutase gene glm M, which is commonly located within the cda A operon in bacteria. The glm M I154F mutation resulted in a lowering of the c-di- AMP level and a reduction in the key peptidoglycan precursor UDP- N-acetylglucosamine in L. lactis. C-di- AMP synthesis by CdaA was shown to be inhibited by GlmMI154F more than GlmM and Glm MI154F was found to bind more strongly to CdaA than GlmM. These findings identify GlmM as a c-di- AMP level modulating protein and provide a direct connection between c-di- AMP synthesis and peptidoglycan biosynthesis.
- Subjects
SECOND messengers (Biochemistry); ADENOSINE monophosphate; PEPTIDOGLYCANS; PHOSPHODIESTERASES; GLYCOASPARAGINASE
- Publication
Molecular Microbiology, 2016, Vol 99, Issue 6, p1015
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/mmi.13281