Abstract
The success of a pathogen depends on its ability for long-term survival under hostile environmental conditions. In this regard, second nucleotide messengers like cyclic di-GMP and cyclic di-AMP play a major role. In mycobacteria, cyclic di-GMP has been shown to be involved in several fundamental phenotypes like cell division, biofilm formation, and antibiotic resistance. Compared to cyclic di-GMP, there is little information available regarding the physiological role of cyclic di-AMP in mycobacteria. However, both these second messengers are associated with the activation of immune response in the host. Most antibiotics target the key pathways of the central dogma, but bacteria evolve to become resistant to them. Therefore, auxiliary pathways, like the stress response pathways, can be putative targets for the development of novel therapeutics. Mycobacterium smegmatis encodes a single gene for cyclic di-GMP metabolism and a single gene each for cyclic di-AMP synthesis and hydrolysis. This makes it an ideal system to gain a deeper insight into the phenotypes affected by cyclic dinucleotides in mycobacteria. In this chapter, we have summarized the recent advances in the field of cyclic dinucleotide signaling in mycobacteria with a focus on their metabolism, regulation of activity, and the diversity of phenotypes governed by them. In the future, the research needs to address the important questions regarding the crosstalk between the second messengers as well as identification of new second messengers in mycobacteria.
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Acknowledgment
We would like to thank the Indian Institute of Science, Bangalore, for funding. DC is grateful to DST J.C. Bose fellowship for funding. AP acknowledges DST for fellowship. AM acknowledges DBT for fellowship. We are also thankful to Sujay Naik for the help with manuscript editing.
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Petchiappan, A., Mahapa, A., Chatterji, D. (2020). Cyclic Dinucleotide Signaling in Mycobacteria. 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_1
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