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Category: Microbial Genetics and Molecular Biology
Cyclic AMP Signaling in Mycobacteria, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818845/9781555818838_Chap14-1.gif /docserver/preview/fulltext/10.1128/9781555818845/9781555818838_Chap14-2.gifAbstract:
The ability to sense and respond to changing environments is essential for all organisms, and this process is mediated through signal transduction. The small molecules that relay signals from receptors to one or more effector proteins within the cell during signal transduction are called second messengers. Cyclic nucleotides, (p)ppGpp, Ca2+, inositol triphosphate, and diacylglycerol function as second messengers in different types of cells. Cyclic 3′,5′-AMP (cAMP) is one of the most widely used second messengers, and its presence in bacteria, archaea, fungi, eukaryotic parasites, and mammals provides numerous opportunities for cAMP-mediated modulation of host-pathogen interactions ( 1 – 5 ).
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Environmental signals to regulatory outputs by cAMP. The conversion of ATP into cAMP and inorganic pyrophosphate and AMP is catalyzed by ACs. Degradation of cAMP is catalyzed by the phosphodiesterase. Activation of the AC can come from extracellular and intracellular signals that are relayed to the AC through membrane-bound or cytoplasmic receptors. The newly generated cAMP relays the activating signal to cAMP-binding proteins.
M. tuberculosis cAMP signaling pathways. ACs are shown with their known signals. Upon activation by the signal, the ACs generate cAMP and there are several fates of cAMP within M. tuberculosis. Most notable is cAMP binding to cNMP binding proteins to affect virulence, gene expression (including macrophage gene expression), and protein lysine acetylation. cAMP can be exported to the macrophage to affect TNFα production. Finally, Rv0805 can decrease cAMP levels by degrading the cAMP. Activating signals are shown in green, cAMP effector proteins are in yellow, and functional outcomes are designated in blue.
cAMP-dependent regulation of acetylation in E. coli (A) and Mycobacterium (B). In E. coli, cAMP's role in regulation is at the transcriptional level, whereas in M. tuberculosis, cAMP binds to the acetyltransferase, PatA, directly. cAMP-CRP complexes regulate acs and patZ at the transcriptional level in E. coli, while the role of CRPMt in regulation of acs and patA is unknown at this time. CobB is a NAD+-dependent sirtuin, as is Rv1151c.
ACs in Mycobacterium