Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis

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 and Turner, Mark S. (2015) Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis. Molecular Microbiology, 99 6: 1015-1027. doi:10.1111/mmi.13281


Author 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.
Title Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis
Journal name Molecular Microbiology   Check publisher's open access policy
ISSN 1365-2958
0950-382X
Publication date 2015-01-01
Year available 2015
Sub-type Article (original research)
DOI 10.1111/mmi.13281
Open Access Status Not yet assessed
Volume 99
Issue 6
Start page 1015
End page 1027
Total pages 13
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted 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 Lactococcus. We characterized suppressor mutations that restored osmoresistance to spontaneous c-di-AMP phosphodiesterase gdpP mutants, which contain high c-di-AMP levels. Loss-of-function and gain-of-function mutations were identified in the cdaA and gdpP genes, respectively, which led to lower c-di-AMP levels. A mutation was also identified in the phosphoglucosamine mutase gene glmM, which is commonly located within the cdaA operon in bacteria. The glmM 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 GlmMI154F 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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