Antifungal action of human cathelicidin fragment (LL13-37) on Candida albicans

Human cathelicidin LL37 and its fragments LL13-37 and LL17-32 exhibited similar potencies in inhibiting growth of the yeast Candida albicans. After treatment with 0.5 mu M and 5 mu M LL13-37, the hyphae changed from a uniformly thick to an increasingly slender appearance, with budding becoming less normal in appearance and cell death could be detected. Only the yeast form and no hyphal form could be observed following exposure to 50 mu M LL13-37. LL13-37 at a concentration of 5 mu M was able to permeabilize the membrane of yeast form as well as hyphal form of C. albicans since the nuclear stain SYTOX Green was localized in both forms. Mycelia treated with LL13-37 stained with SYTOX Green, but did not stain with MitoTracker deep red, indicating that the mitochondria were adversely affected by LL13-37. Bimane-labeled LL13-37 was able to enter some of the hyphae, but not all hyphae were affected, suggesting that LL37impaired membrane permeability characteristics in some of the hyphae. Reactive oxygen species was detectable in the yeast form of C. albicans cells after treatment with LL13-37 but not in the untreated cells. The results suggest that the increased membrane permeability caused by LL13-37 might not be the sole cause of cell death. It might lead to the uptake of the peptide, which might have some intracellular targets. (C) 2011 Elsevier Inc. All rights reserved.