Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase

Nisheeth Agarwal, Gyanu Lamichhane, Radhika Gupta, Scott Nolan and William R. Bishai ()
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Nisheeth Agarwal: Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA
Gyanu Lamichhane: Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA
Radhika Gupta: Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA
Scott Nolan: Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA
William R. Bishai: Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA

Nature, 2009, vol. 460, issue 7251, 98-102

Abstract: Tuberculosis virulence factor A previously unknown virulence mechanism has been identified for Mycobacterium tuberculosis: intoxication of host macrophages by bacterial-derived cyclic AMP. It was known that M. tuberculosis induces increased cyclic AMP levels in infected macrophages; this cyclic AMP is now shown to be produced by bacterial adenylate cyclase, and to enhance virulence presumably through the activation of downstream signalling pathways. The cyclic AMP stimulates host TNF-α (tumour necrosis factor-α) and causes more extensive liver disease and improved bacterial survival in infected mice. This work highlights signal transduction interference by M. tuberculosis as a possible new target for antituberculosis drugs.

Date: 2009
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DOI: 10.1038/nature08123

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