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Cyclic di-AMP Signaling in Streptococcus pneumoniae

  • Tiffany M. Zarrella
  • Guangchun BaiEmail author
Chapter

Abstract

Streptococcus pneumoniae causes diseases such as pneumonia, otitis media, meningitis, and bacteremia. As such, this pathogen survives and adapts to different environmental stimuli and withstands stress conditions encountered during colonization, dissemination, and infection in the respective host compartments. Recent studies designate the bacterial signaling nucleotide cyclic di-adenosine monophosphate (cyclic di-AMP) as an important facet to pneumococcal physiology and virulence. In this chapter, we will describe the signaling network and the role of cyclic di-AMP as a second messenger in pneumococci. In S. pneumoniae, cyclic di-AMP is produced by a sole diadenylate cyclase, CdaA, and is catabolized by two phosphodiesterases, Pde1 and Pde2. cyclic di-AMP is secreted through an unidentified mechanism which may impact host–pathogen interactions. The gene encoding CdaA is essential, and perturbation of cyclic di-AMP levels affects adaptation to stress, epithelial cell adhesion, and pneumococcal virulence, demonstrating that cyclic di-AMP is a pervasive molecule in pathogenesis. A Trk-family cyclic di-AMP binding protein, CabP, has been characterized as a mediator of potassium uptake via the transporter TrkH. Potassium levels affect expression of CdaA, and CabP modulates cyclic di-AMP homeostasis, suggesting that cyclic di-AMP plays a fundamental role in ion transport. Nevertheless, repercussions of cyclic di-AMP signaling discussed here allude to the existence of additional cyclic di-AMP effectors. Future avenues of research and outlying questions of interest are addressed.

Keywords

Streptococcus pneumoniae Cyclic di-AMP Stress response CdaA Pde1 Pde2 CabP TrkH 

Notes

Acknowledgments

The writing of this chapter by TZ was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. GB is a subrecipient of NIH grant R35HL135756.

Conflict of Interest

The authors declare no conflict of interest.

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Laboratory of Molecular Biology, Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  2. 2.Department of Immunology and Microbial DiseaseAlbany Medical CollegeAlbanyUSA

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