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 Previous Article

Microbiology and Molecular Biology Reviews, December 2008, p. 765-781, Vol. 72, No. 4
1092-2172/08/$08.00+0     doi:10.1128/MMBR.00013-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Fiona M. Sansom,1 Simon C. Robson,2 and Elizabeth L. Hartland1*

Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia,1 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 022152

Summary: In humans, purinergic signaling plays an important role in the modulation of immune responses through specific receptors that recognize nucleoside tri- and diphosphates as signaling molecules. Ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTPDases) have important roles in the regulation of purinergic signaling by controlling levels of extracellular nucleotides. This process is key to pathophysiological protective responses such as hemostasis and inflammation. Ecto-NTPDases are found in all higher eukaryotes, and recently it has become apparent that a number of important parasitic pathogens of humans express surface-located NTPDases that have been linked to virulence. For those parasites that are purine auxotrophs, these enzymes may play an important role in purine scavenging, although they may also influence the host response to infection. Although ecto-NTPDases are rare in bacteria, expression of a secreted NTPDase in Legionella pneumophila was recently described. This ecto-enzyme enhances intracellular growth of the bacterium and potentially affects virulence. This discovery represents an important advance in the understanding of the contribution of other microbial NTPDases to host-pathogen interactions. Here we review other progress made to date in the characterization of ecto-NTPDases from microbial pathogens, how they differ from mammalian enzymes, and their association with organism viability and virulence. In addition, we postulate how ecto-NTPDases may contribute to the host-pathogen interaction by reviewing the effect of selected microbial pathogens on purinergic signaling. Finally, we raise the possibility of targeting ecto-NTPDases in the development of novel anti-infective agents based on potential structural and clear enzymatic differences from the mammalian ecto-NTPDases.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Grattan St., Parkville, Victoria 3010, Australia. Phone: 61-3-8344-8041. Fax: 61-3-9347-1540. E-mail: hartland{at}unimelb.edu.au

Microbiology and Molecular Biology Reviews, December 2008, p. 765-781, Vol. 72, No. 4
1092-2172/08/$08.00+0     doi:10.1128/MMBR.00013-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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