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Cyclic di-AMP Signaling in Streptococcus pneumoniae

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Microbial Cyclic Di-Nucleotide Signaling

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.

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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.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Tiffany M. Zarrella

  2. Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA

    Guangchun Bai

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  1. Tiffany M. Zarrella
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  2. Guangchun Bai
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Correspondence to Guangchun Bai .

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Editors and Affiliations

  1. Institute of Biochemistry and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan

    Shan-Ho Chou

  2. Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile

    Nicolas Guiliani

  3. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA

    Vincent T. Lee

  4. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    Ute Römling

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Zarrella, T.M., Bai, G. (2020). Cyclic di-AMP Signaling in Streptococcus pneumoniae . In: Chou, SH., Guiliani, N., Lee, V., Römling, U. (eds) Microbial Cyclic Di-Nucleotide Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-33308-9_27

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