Cyclic AMP signalling in mycobacteria: Redirecting the conversation with a common currency

Wadsworth Center, New York State Department of Health, Albany, NY 12201-2002, USA.
Cellular Microbiology (Impact Factor: 4.92). 03/2011; 13(3):349-58. DOI: 10.1111/j.1462-5822.2010.01562.x
Source: PubMed


cAMP is an ancient second messenger, and is used by many organisms to regulate a wide range of cellular functions. Mycobacterium tuberculosis complex bacteria are exceptional in that they have genes for at least 15 biochemically distinct adenylyl cyclases, the enzymes that generate cAMP. cAMP-associated gene regulation within tubercle bacilli is required for their virulence, and secretion of cAMP produced by M. tuberculosis bacteria into host macrophages disrupts the host's immune response to infection. In this review, we discuss recent advances in our understanding of the means by which cAMP levels are controlled within mycobacteria, the importance of cAMP to M. tuberculosis during host infection, and the role of cAMP in mycobacterial gene regulation. Understanding the myriad aspects of cAMP signalling in tubercle bacilli will establish new paradigms for cAMP signalling, and may contribute to new approaches for prevention and/or treatment of tuberculosis disease.

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    • "The phagolysosome is an acidic, nutrient poor, and oxidatively hostile environment, and bacteria slow down their metabolism to survive [42]. When M. tuberculosis is phagocyted by macrophages, cAMP increases dramatically, and this cAMP is secreted to the phagolysosome, exerting responses in the host which are involved in pathogenesis [43]. "
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    • "Analysis of the M. tuberculosis H37Rv genome has identified 15 genes and one pseudogene that encode for proteins with predicted AC domains (Shenoy and Visweswariah 2006). Many of the AC present in M. tuberculosis have been biochemically characterized and reviews regarding them have been recently published (Shenoy et al. 2004; Barba et al. 2010; Bai et al. 2011). Despite this characterization, only few of the AC have been associated with the physiology of the slow-growing mycobacteria to date. "
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    • "Cellular concentration of cAMP can be regulated at the level of expression and/or activity of AC and the PDE, or by a change in the rate of cAMP export [6], [32]–[34]. Although intracellular cAMP levels are significantly altered in Mtb, we observed that the extracellular cAMP pool remains constant over eight days of in vitro growth (data not shown). "
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