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Cyclic di-AMP regulation of osmotic homeostasis is essential in Group B Streptococcus.
- Source :
-
PLoS genetics [PLoS Genet] 2018 Apr 16; Vol. 14 (4), pp. e1007342. Date of Electronic Publication: 2018 Apr 16 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Cyclic nucleotides are universally used as secondary messengers to control cellular physiology. Among these signalling molecules, cyclic di-adenosine monophosphate (c-di-AMP) is a specific bacterial second messenger recognized by host cells during infections and its synthesis is assumed to be necessary for bacterial growth by controlling a conserved and essential cellular function. In this study, we sought to identify the main c-di-AMP dependent pathway in Streptococcus agalactiae, the etiological agent of neonatal septicaemia and meningitis. By conditionally inactivating dacA, the only diadenyate cyclase gene, we confirm that c-di-AMP synthesis is essential in standard growth conditions. However, c-di-AMP synthesis becomes rapidly dispensable due to the accumulation of compensatory mutations. We identified several mutations restoring the viability of a ΔdacA mutant, in particular a loss-of-function mutation in the osmoprotectant transporter BusAB. Identification of c-di-AMP binding proteins revealed a conserved set of potassium and osmolyte transporters, as well as the BusR transcriptional factor. We showed that BusR negatively regulates busAB transcription by direct binding to the busAB promoter. Loss of BusR repression leads to a toxic busAB expression in absence of c-di-AMP if osmoprotectants, such as glycine betaine, are present in the medium. In contrast, deletion of the gdpP c-di-AMP phosphodiesterase leads to hyperosmotic susceptibility, a phenotype dependent on a functional BusR. Taken together, we demonstrate that c-di-AMP is essential for osmotic homeostasis and that the predominant mechanism is dependent on the c-di-AMP binding transcriptional factor BusR. The regulation of osmotic homeostasis is likely the conserved and essential function of c-di-AMP, but each species has evolved specific c-di-AMP mechanisms of osmoregulation to adapt to its environment.
- Subjects :
- ATP-Binding Cassette Transporters genetics
ATP-Binding Cassette Transporters metabolism
Bacterial Proteins genetics
Bacterial Proteins metabolism
Genes, Bacterial
Homeostasis physiology
Host-Pathogen Interactions physiology
Humans
Mutation
Osmoregulation genetics
Phosphorus-Oxygen Lyases genetics
Phosphorus-Oxygen Lyases metabolism
Potassium metabolism
Second Messenger Systems physiology
Streptococcus agalactiae genetics
Streptococcus agalactiae growth & development
Dinucleoside Phosphates metabolism
Osmoregulation physiology
Streptococcus agalactiae metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 29659565
- Full Text :
- https://doi.org/10.1371/journal.pgen.1007342