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Cyclic AMP Signaling in Mycobacteria

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  • Authors: Gwendowlyn S. Knapp1, Kathleen A. McDonough2
  • Editors: Graham F. Hatfull4, William R. Jacobs Jr.5
    Affiliations: 1: Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, Albany, NY 12222; 2: Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, Albany, NY 12222; 3: Department of Biomedical Sciences, University at Albany, Albany, NY 12222; 4: University of Pittsburgh, Pittsburgh, PA 15260; 5: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461
  • Source: microbiolspec April 2014 vol. 2 no. 2 doi:10.1128/microbiolspec.MGM2-0011-2013
  • Received 29 August 2013 Accepted 04 September 2013 Published 04 April 2014
  • K. A. McDonough, [email protected]orth.org
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  • Abstract:

    All cells must adapt to changing conditions, and many use cyclic AMP (cAMP) as a second messenger to sense and respond to fluctuations in their environment. cAMP is made by adenylyl cyclases (ACs), and mycobacteria have an unusually large number of biochemically distinct ACs. cAMP is important for gene regulation in mycobacteria, and the ability to secrete cAMP into host macrophages during infection contributes to pathogenesis. This article discusses the many roles of cAMP in mycobacteria and reviews what is known about the factors that contribute to production, destruction, and utilization of this important signal molecule. Special emphasis is placed on cAMP signaling in complex bacteria and its importance to during host infection.

  • Citation: Knapp G, McDonough K. 2014. Cyclic AMP Signaling in Mycobacteria. Microbiol Spectrum 2(2):MGM2-0011-2013. doi:10.1128/microbiolspec.MGM2-0011-2013.


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All cells must adapt to changing conditions, and many use cyclic AMP (cAMP) as a second messenger to sense and respond to fluctuations in their environment. cAMP is made by adenylyl cyclases (ACs), and mycobacteria have an unusually large number of biochemically distinct ACs. cAMP is important for gene regulation in mycobacteria, and the ability to secrete cAMP into host macrophages during infection contributes to pathogenesis. This article discusses the many roles of cAMP in mycobacteria and reviews what is known about the factors that contribute to production, destruction, and utilization of this important signal molecule. Special emphasis is placed on cAMP signaling in complex bacteria and its importance to during host infection.

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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.

Source: microbiolspec April 2014 vol. 2 no. 2 doi:10.1128/microbiolspec.MGM2-0011-2013
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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 . 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.

Source: microbiolspec April 2014 vol. 2 no. 2 doi:10.1128/microbiolspec.MGM2-0011-2013
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cAMP-dependent regulation of acetylation in and . In , cAMP's role in regulation is at the transcriptional level, whereas in cAMP binds to the acetyltransferase, PatA, directly. cAMP-CRP complexes regulate and Z at the transcriptional level in while the role of CRP in regulation of and A is unknown at this time. CobB is a NAD-dependent sirtuin, as is Rv1151c.

Source: microbiolspec April 2014 vol. 2 no. 2 doi:10.1128/microbiolspec.MGM2-0011-2013
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ACs in

Source: microbiolspec April 2014 vol. 2 no. 2 doi:10.1128/microbiolspec.MGM2-0011-2013

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