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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Bacterial second messenger cyclic di-AMP in streptococci.

Michael J Wright1, Guangchun Bai2

  • 1Department of Internal Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.

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|October 28, 2023
PubMed
Summary

Cyclic dimeric adenosine monophosphate (c-di-AMP) is a key signaling molecule in Streptococcus bacteria, impacting growth, pathogenesis, and host immunity. This review details c-di-AMP networks across seven species, highlighting its diverse roles.

Keywords:
Streptococcusc-di-AMPc-di-AMP phosphodiesterasec-di-AMP-binding proteindiadenylate cyclasetype I interferon

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Pathogenesis

Background:

  • Cyclic dimeric adenosine monophosphate (c-di-AMP) is a crucial secondary messenger in bacteria, first identified in 2008.
  • Streptococcus species utilize a unique adenylyl cyclase (CdaA) and phosphodiesterases for c-di-AMP metabolism.
  • The essentiality of cdaA varies among Streptococcus species under standard laboratory conditions.

Purpose of the Study:

  • To review and consolidate the known c-di-AMP signaling networks in seven distinct Streptococcus species.
  • To elucidate the diverse biological functions influenced by c-di-AMP in these streptococci.
  • To explore the implications of streptococcal c-di-AMP in host-pathogen interactions and immune responses.

Main Methods:

  • Literature review of studies on c-di-AMP in Streptococcus species.
  • Comparative analysis of c-di-AMP pathway components (CdaA, phosphodiesterases, effectors) across species.
  • Synthesis of data on c-di-AMP's role in bacterial physiology and pathogenesis.

Main Results:

  • Streptococci possess specific c-di-AMP cyclases and phosphodiesterases, with varying dependence on cdaA for viability.
  • c-di-AMP influences critical bacterial processes including growth, morphology, biofilm formation, drug resistance, and pathogenesis.
  • Secreted c-di-AMP from streptococci can modulate mammalian host immune responses, notably inducing type I interferon production.

Conclusions:

  • c-di-AMP signaling is a versatile regulatory system in Streptococcus, contributing to diverse phenotypes and clinical manifestations.
  • Understanding these c-di-AMP networks is vital for deciphering streptococcal virulence and host interactions.
  • Future research should focus on further characterizing c-di-AMP's role in these significant bacterial pathogens.