Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant.
The broadly conserved bacterial signalling molecule cyclic-di-adenosine monophosphate (c-di-AMP) controls osmoresistance via its regulation of potassium (K+) and compatible solute uptake. High levels of c-di-AMP resulting from inactivation of c-di-AMP phosphodiesterase activity leads to poor growth...
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2018-08-01
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doaj-b18b53e2941a40ed99bddeff8d3a0c372020-11-24T21:41:58ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-08-01148e100757410.1371/journal.pgen.1007574Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant.Huong Thi PhamNguyen Thi Hanh NhiepThu Ngoc Minh VuTuAnh Ngoc HuynhYan ZhuAnh Le Diep HuynhAlolika ChakraborttiEsteban MarcellinRaquel LoChristopher B HowardNidhi BansalJoshua J WoodwardZhao-Xun LiangMark S TurnerThe broadly conserved bacterial signalling molecule cyclic-di-adenosine monophosphate (c-di-AMP) controls osmoresistance via its regulation of potassium (K+) and compatible solute uptake. High levels of c-di-AMP resulting from inactivation of c-di-AMP phosphodiesterase activity leads to poor growth of bacteria under high osmotic conditions. To better understand how bacteria can adjust in response to excessive c-di-AMP levels and to identify signals that feed into the c-di-AMP network, we characterised genes identified in a screen for osmoresistant suppressor mutants of the high c-di-AMP Lactococcus ΔgdpP strain. Mutations were identified which increased the uptake of osmoprotectants, including gain-of-function mutations in a Kup family K+ importer (KupB) and inactivation of the glycine betaine transporter transcriptional repressor BusR. The KupB mutations increased the intracellular K+ level while BusR inactivation increased the glycine betaine level. In addition, BusR was found to directly bind c-di-AMP and repress expression of the glycine betaine transporter in response to elevated c-di-AMP. Interestingly, overactive KupB activity or loss of BusR triggered c-di-AMP accumulation, suggesting turgor pressure changes act as a signal for this second messenger. In another group of suppressors, overexpression of an operon encoding an EmrB family multidrug resistance protein allowed cells to lower their intracellular level of c-di-AMP through active export. Lastly evidence is provided that c-di-AMP levels in several bacteria are rapidly responsive to environmental osmolarity changes. Taken together, this work provides evidence for a model in which high c-di-AMP containing cells are dehydrated due to lower K+ and compatible solute levels and that this osmoregulation system is able to sense and respond to cellular water stress.http://europepmc.org/articles/PMC6108528?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huong Thi Pham Nguyen Thi Hanh Nhiep Thu Ngoc Minh Vu TuAnh Ngoc Huynh Yan Zhu Anh Le Diep Huynh Alolika Chakrabortti Esteban Marcellin Raquel Lo Christopher B Howard Nidhi Bansal Joshua J Woodward Zhao-Xun Liang Mark S Turner |
spellingShingle |
Huong Thi Pham Nguyen Thi Hanh Nhiep Thu Ngoc Minh Vu TuAnh Ngoc Huynh Yan Zhu Anh Le Diep Huynh Alolika Chakrabortti Esteban Marcellin Raquel Lo Christopher B Howard Nidhi Bansal Joshua J Woodward Zhao-Xun Liang Mark S Turner Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. PLoS Genetics |
author_facet |
Huong Thi Pham Nguyen Thi Hanh Nhiep Thu Ngoc Minh Vu TuAnh Ngoc Huynh Yan Zhu Anh Le Diep Huynh Alolika Chakrabortti Esteban Marcellin Raquel Lo Christopher B Howard Nidhi Bansal Joshua J Woodward Zhao-Xun Liang Mark S Turner |
author_sort |
Huong Thi Pham |
title |
Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. |
title_short |
Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. |
title_full |
Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. |
title_fullStr |
Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. |
title_full_unstemmed |
Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. |
title_sort |
enhanced uptake of potassium or glycine betaine or export of cyclic-di-amp restores osmoresistance in a high cyclic-di-amp lactococcus lactis mutant. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2018-08-01 |
description |
The broadly conserved bacterial signalling molecule cyclic-di-adenosine monophosphate (c-di-AMP) controls osmoresistance via its regulation of potassium (K+) and compatible solute uptake. High levels of c-di-AMP resulting from inactivation of c-di-AMP phosphodiesterase activity leads to poor growth of bacteria under high osmotic conditions. To better understand how bacteria can adjust in response to excessive c-di-AMP levels and to identify signals that feed into the c-di-AMP network, we characterised genes identified in a screen for osmoresistant suppressor mutants of the high c-di-AMP Lactococcus ΔgdpP strain. Mutations were identified which increased the uptake of osmoprotectants, including gain-of-function mutations in a Kup family K+ importer (KupB) and inactivation of the glycine betaine transporter transcriptional repressor BusR. The KupB mutations increased the intracellular K+ level while BusR inactivation increased the glycine betaine level. In addition, BusR was found to directly bind c-di-AMP and repress expression of the glycine betaine transporter in response to elevated c-di-AMP. Interestingly, overactive KupB activity or loss of BusR triggered c-di-AMP accumulation, suggesting turgor pressure changes act as a signal for this second messenger. In another group of suppressors, overexpression of an operon encoding an EmrB family multidrug resistance protein allowed cells to lower their intracellular level of c-di-AMP through active export. Lastly evidence is provided that c-di-AMP levels in several bacteria are rapidly responsive to environmental osmolarity changes. Taken together, this work provides evidence for a model in which high c-di-AMP containing cells are dehydrated due to lower K+ and compatible solute levels and that this osmoregulation system is able to sense and respond to cellular water stress. |
url |
http://europepmc.org/articles/PMC6108528?pdf=render |
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