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Cyclic di-AMP in Mycobacterium tuberculosis

  • Yinlan Bai
  • Guangchun BaiEmail author
Chapter
  • 114 Downloads

Abstract

Mycobacterium tuberculosis (Mtb) is the etiologic agent of tuberculosis (TB), which is the leading cause of death worldwide by a single bacterial pathogen. This bacterium encodes a diadenylate cyclase, which is a homolog of Bacillus subtilis DNA integrity scanning protein A (DisA) and converts ATP into cyclic di-adenosine monophosphate (cyclic di-AMP). Mtb also possesses a DHH/DHHA1 family cyclic di-AMP phosphodiesterase, CnpB, which degrades cyclic di-AMP into AMP. Interestingly, elevating cyclic di-AMP levels by either overexpression of Mtb disA or deletion of cnpB in this pathogen results in significant virulence attenuation in a mouse pulmonary TB model. It has also been shown that cyclic di-AMP from Mtb activates autophagy and limits the growth of bacteria within infected cells. These findings indicate that cyclic di-AMP plays an important role in TB pathogenesis. Mtb exports cyclic di-AMP via an undefined mechanism, which induces a type I interferon response in a STING-dependent manner within the infected host. In contrast, the current live vaccine strain M. bovis BCG is unable to secrete cyclic di-AMP and is defective in inducing a type I interferon response. Thus, enabling the vaccine strain to induce type I interferon may provide better protection against infection of Mtb.

Keywords

Mycobacterium tuberculosis Cyclic di-AMP DisA CnpB Pathogenesis Type I interferon Vaccine 

Notes

Conflict of Interest

The authors declare no conflict of interest.

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Microbiology, College of Basic Medical SciencesAir Force Military Medical UniversityXi’anChina
  2. 2.Department of Immunology and Microbial DiseaseAlbany Medical CollegeAlbanyUSA

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