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Cyclic‐di‐ AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in L actococcus lactis
Author(s) -
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 ZhaoXun,
Turner Mark S.
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13281
Subject(s) - biology , peptidoglycan , mutant , operon , cyclase , biochemistry , adenylate kinase , biosynthesis , enzyme , gene
Summary 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 F irmicutes 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 GlmM I154F more than GlmM and Glm M I154F 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.