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Antimicrobial Agents and Chemotherapy, September 2004, p. 3367-3372, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3367-3372.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Tear Lipocalin Exhibits Antimicrobial Activity by Scavenging Microbial Siderophores

Department of Molecular Biology, Innsbruck Medical University, Innsbruck, Austria,¹ Department of Pathology and Ophthalmology, Jules Stein Eye Institute, School of Medicine, University of California at Los Angeles, Los Angeles, California²

Received 3 February 2004/ Returned for modification 19 March 2004/ Accepted 3 May 2004

Human tear lipocalin (TL; also known as Lcn1) is a secretory protein present in large amounts in fluids that cover epithelial surfaces such as tears and respiratory secretions. It is supposed to act as a physiological scavenger of hydrophobic, potentially harmful molecules, but there is evidence that it also inhibits bacterial growth. In the present study, we reconsidered the possibility that TL might interfere with microbial growth by scavenging of siderophores, as described for human neutrophil gelatinase-associated lipocalin (NGAL). Indeed, our experiments revealed that TL binds to microbial siderophores with high affinities. In contrast to NGAL, which was shown to have some specificity for bacterial catecholate-type siderophores, TL binds to a broad array of siderophores, including bacterial catecholate-type enterobactin and hydroxamate-type desferrioxamine B, and all major classes of fungal siderophores. By adding exogenous TL, bacterial and fungal growth could be inhibited under iron-limiting conditions. Thus, TL might be a novel member of the innate immune system especially involved in mucosal defense against fungal infections.

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