Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores.
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.
Department of Molecular Biology, Innsbruck Medical University, Peter-Mayr Strasse 4b, A-6020 Innsbruck, Austria.
Maria
M
Fluckinger
Hubertus
H
Haas
Petra
P
Merschak
Ben J
BJ
Glasgow
Bernhard
B
Redl
D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D003470:Culture Media; D005227:Fatty Acids / Q000378:metabolism; D005658:Fungi / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D008024:Ligands; D054835:Lipocalin 1; D000071068:Lipocalin-2; D054834:Lipocalins; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017262:Siderophores / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D013666:Tears / Q000737:chemistry*
D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002352:Carrier Proteins; D003470:Culture Media; D005227:Fatty Acids; C518443:LCN1 protein, human; C489506:LCN2 protein, human; D008024:Ligands; D054835:Lipocalin 1; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017262:Siderophores