This Article Full Text (PDF) Other Versions of this Article: AAC.00585-07v1 52/2/483    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bellemare, A. Articles by Bourbonnais, Y. Search for Related Content PubMed PubMed Citation Articles by Bellemare, A. Articles by Bourbonnais, Y.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.00585-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

HUMAN PRE-ELAFIN INHIBITS A PSEUDOMONAS AERUGINOSA SECRETED PEPTIDASE AND PREVENTS ITS PROLIFERATION IN COMPLEX MEDIA

From the Département de biochimie et de microbiologie and Centre de recherche sur la fonction, la structure et l'ingénierie des protéines (CREFSIP), Université Laval, Québec, Qc, Canada

^* To whom correspondence should be addressed. Email: Yves.Bourbonnais{at}bcm.ulaval.ca.

	Abstract

Pseudomonas aeruginosa is a life-threatening opportunist human pathogen frequently associated with lung inflammatory diseases, and namely cystic fibrosis. Like other species, this Gram-negative bacteria is increasingly drug resistant. During the past decade, intensive research efforts have been focused on the identification of natural innate defense molecules with broad antimicrobial activities, collectively known as antimicrobial peptides (AMP). Human pre-elafin, best characterized as a potent inhibitor of neutrophil elastase with anti-inflammatory properties, was also shown to possess antimicrobial activity against both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. Its mode of action was, however, not known. Using full-length pre-elafin, each domain separately, and mutated variants of pre-elafin with attenuated antipeptidase activity toward neutrophil elastase, we report here that both pre-elafin domains contribute, through distinct mechanisms, to its antibacterial activity against Pseudomonas aeruginosa. Most importantly, we demonstrate that the WAP domain specifically inhibits a secreted peptidase having the characteristics of arginyl peptidase (protease IV). This is the first demonstration that a human WAP-motif protein inhibits a secreted peptidase to prevent bacterial growth in vitro. Since several WAP-motif proteins from various species demonstrate antimicrobial function with variable activities toward bacterial species, we suggest that this mechanism may be more common than initially anticipated.