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Cited by 100Bacterial Genetics and BiotechnologyBiochemical and Molecular ResearchDrug Transport and Resistance Mechanisms

Cyclic di‐AMP targets the cystathionine beta‐synthase domain of the osmolyte transporter OpuC

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Huynh, TuAnh Ngoc, Choi, Philip H., Sureka, Kamakshi, Ledvina, Hannah E., Campillo, Julian, Tong, Liang, Woodward, Joshua J.·2016·Molecular Microbiology
DOI 10.1111/mmi.13456PMC PMC5118871
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Abstract

Summary: Cellular turgor is of fundamental importance to bacterial growth and survival. Changes in external osmolarity as a consequence of fluctuating environmental conditions and colonization of diverse environments can significantly impact cytoplasmic water content, resulting in cellular lysis or plasmolysis. To ensure maintenance of appropriate cellular turgor, bacteria import ions and small organic osmolytes, deemed compatible solutes, to equilibrate cytoplasmic osmolarity with the extracellular environment. Here, we show that elevated levels of c‐di‐AMP, a ubiquitous second messenger among bacteria, result in significant susceptibility to elevated osmotic stress in the bacterial pathogen Listeria monocytogenes . We found that levels of import of the compatible solute carnitine show an inverse correlation with intracellular c‐di‐AMP content and that c‐di‐AMP directly binds to the CBS domain of the ATPase subunit of the carnitine importer OpuC. Biochemical and structural studies identify conserved residues required for this interaction and transport activity in bacterial cells. Overall, these studies reveal a role for c‐di‐AMP mediated regulation of compatible solute import and provide new insight into the molecular mechanisms by which this essential second messenger impacts bacterial physiology and adaptation to changing environmental conditions.

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  • The pgpH gdpP double mutant was not rescued by glycine betaine.

    “Interestingly, and consistent with the established inhibition of compatible solute import by c-di-AMP (35, 39, 40), the pgpH gdpP double mutant was not rescued by GB (Fig. S4B).”

    From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [40]

    The Results section (‘C-di-AMP accumulation diminishes compatible solute uptake’; page unavailable) reports that betaine did not rescue the salt-stressed L. monocytogenes ΔpdeA ΔpgpH mutant. It does not report this result for a pgpH gdpP double mutant. In the citing sentence, the citations support the background point about c-di-AMP inhibiting compatible-solute import; the mutant-rescue result is attributed to the citing paper’s Fig. S4B. (LLM, conf=0.84)

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Research works printed but not linked: 54

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Authors
Huynh, T. N., Choi, P. H., Sureka, K., Ledvina, H. E., Campillo, J., Tong, L., & Woodward, J. J.
Affiliations
  • University of Washington (US)
  • Columbia University (US)
Corresponding author
  • Tong, Liang
  • Woodward, Joshua J.
ORCID
Venue
Molecular Microbiology
Publisher
Wiley
Published
2016-07-26
Volume
102
Issue
2
Pages
233-243
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
DOI
10.1111/mmi.13456
PMC
PMC5118871
OpenAlex
W2467467244
Cited by
100
References
0
Citations by year
2026: 3 · 2025: 5 · 2024: 10 · 2023: 14 · 2022: 10 · 2021: 12 · 2020: 15 · 2019: 12 · 2018: 7 · 2017: 9 · 2016: 3
FWCI
8.35
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Molecular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1s10od012018-01a1)
  • National Institute of Allergy and Infectious Diseases (R01AI116669, T32AI055396)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
cyclic di-AMP, cystathionine beta-synthase domain, Listeria monocytogenes, osmolytes, osmolyte transport, osmotic stress, second messenger signaling, ATPase
MeSH terms
Cyclic AMP, Adenosine Monophosphate, Bacterial Proteins, Betaine, Biological Transport, Active, Carnitine, Cystathionine beta-Synthase, Listeria monocytogenes, Osmolar Concentration, Osmotic Pressure, Dinucleoside Phosphates, ATP-Binding Cassette Transporters

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