Cyclic nucleotide signaling in Mycobacterium tuberculosis: an expanding repertoire

Abstract

Mycobacterium tuberculosis (Mtb) is one of the most successful microbial pathogens, and currently infects over a quarter of the world's population. Mtb's success depends on the ability of the bacterium to sense and respond to dynamic and hostile environments within the host, including the ability to regulate bacterial metabolism and interactions with the host immune system. One of the ways Mtb senses and responds to conditions it faces during infection is through the concerted action of multiple cyclic nucleotide signaling pathways. This review will describe how Mtb uses cyclic AMP, cyclic di-AMP and cyclic di-GMP to regulate important physiological processes, and how these signaling pathways can be exploited for the development of novel thereapeutics and vaccines.

Cyclic oligoadenylate signalling mediates Mycobacterium tuberculosis CRISPR defence

“…Recent discoveries of novel cyclic trinucleotides synthesiszed by bacterial cGAS-like enzymes and detected by vertebrate innate immune surveillance proteins (41,42) make this question pertinent. This is particularly true for organisms such as M. tuberculosis , which has an intracellular lifestyle in vertebrate hosts with which it participates in a two-way communication via cyclic nucleotides (43,44). Furthermore, the significant quantities of nanoRNAs (eg A 3 -triphosphate) synthesized by the Csm complex should not be discounted as dead-end side products.…”

Acanthamoeba castellanii as a Screening Tool for Mycobacterium avium Subspecies paratuberculosis Virulence Factors with Relevance in Macrophage Infection

“…The c-di-GMP and cAMP signaling molecules are second messengers that respond to and control expression of a variety of environmental and quorum sensing signals that bacteria cannot directly internalize, and support microbial transition between motility and surface-associated sessility [ 58 ], including biofilm formation and biofilm-associated motilities in opportunistic human pathogens such as Pseudomonas aeruginosa, Escherichia coli , Staphylococcus aureus, and Salmonella typhimurium [ 56 , 59 , 60 ]. The cyclic di-GMP signaling system regulate several key virulence processes required for bacterial adaptation during the host infection and the evasion of the host immune system, and has been implicated in pathogenesis of Vibrio cholerae , Borrelia burgdorferi , Pseudomonas aeruginosa, Yersinia pestis, Clostridium perfringens, and M. tuberculosis [ 61 , 62 , 63 , 64 ]. The induction of c-di-GMP signaling pathway does not affect aerobic growth of M .…”

Rv2577 of Mycobacterium tuberculosis Is a Virulence Factor With Dual Phosphatase and Phosphodiesterase Functions

“…Regarding physiological substrates, mPDE is more active toward phosphodiester compounds as the second messengers 3 ,5 -cyclic AMP and cyclic-GMP (Shenoy et al, 2005) and 2 ,3 -cAMP (Keppetipola and Shuman, 2008). Interestingly, the Mtb genome contains 13 genes for adenylyl cyclases, being mPDE the unique PDE that allows the maintenance of a correct cAMP homeostasis in the bacterium (Johnson and McDonough, 2018). In addition, YmdB from B. subtilis has the same structure domain and kinetic characteristic than mPDE and both enzymes share the same catalytic activity toward 3 ,5 -cyclic AMP/cGMP and their preference for 2 ,3 -cAMP and 2 ,3 -cGMP compounds (Diethmaier et al, 2014).…”