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    The Human Cathelicidin Antimicrobial Peptide LL-37 Promotes the Growth of the Pulmonary Pathogen Aspergillus fumigatus


    Sheehan, Gerard and Bergsson, Gudmundur and McElvaney, Noel G. and Reeves, Emer P. and Kavanagh, Kevin (2018) The Human Cathelicidin Antimicrobial Peptide LL-37 Promotes the Growth of the Pulmonary Pathogen Aspergillus fumigatus. Infection and Immunity, 86 (7). ISSN 0019-9567

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    Abstract

    The pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the cathelicidin antimicrobial peptide LL-37, and the aim of this work was to assess the effect of LL-37 on the growth of Aspergillus fumigatus, a common pathogen of CF patients. Exposure of A. fumigatus to LL-37 and its derived fragment RK-31 (1.95 μg/ml) for 24 h had a positive effect on growth (199.94% ± 6.172% [P < 0.05] and 218.20% ± 4.63% [P < 0.05], respectively), whereas scrambled LL-37 peptide did not (85.12% ± 2.92%). Exposure of mycelium (preformed for 24 h) to 5 μg/ml intact LL-37 for 48 h increased hyphal wet weight (4.37 ± 0.23 g, P < 0.001) compared to the control (2.67 ± 0.05 g) and scrambled LL-37 (2.23 ± 0.09 g) treatments. Gliotoxin secretion from LL-37 exposed hyphae (169.1 ± 6.36 ng/mg hyphae, P < 0.05) was increased at 24 h compared to the results seen with the control treatment (102 ± 18.81 ng/mg hyphae) and the scrambled LL-37 treatment (96.09 ± 15.15 ng/mg hyphae). Shotgun proteomic analysis of 24-h LL-37-treated hyphae revealed an increase in the abundance of proteins associated with growth (eukaryotic translation initiation factor 5A [eIF-5A] [16.3-fold increased]), tissue degradation (aspartic endopeptidase [4.7-fold increased]), and allergic reactions (Asp F13 [10-fold increased]). By 48 h, there was an increase in protein levels indicative of cellular stress (glutathione peroxidase [9-fold increased]), growth (eIF-5A [6-fold increased]), and virulence (RNase mitogillin [3.7-fold increased]). These results indicate that LL-37 stimulates A. fumigatus growth and that this stimulation can result in increased fungal growth and secretion of toxins in the lungs of CF patients.

    Item Type: Article
    Keywords: Aspergillus fumigatus; antimicrobial peptide; cathelicidin; LL-37; cystic fibrosis; innate immunity;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12446
    Identification Number: https://doi.org/10.1128/IAI.00097-18
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 18 Feb 2020 15:06
    Journal or Publication Title: Infection and Immunity
    Publisher: American Society of Microbiology
    Refereed: Yes
    URI:

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