The Cathelicidin antimicrobial peptide (LL-37) stimulates the growth and pathogenicity of the pulmonary lung pathogen Aspergillus fumigatus

The pulmonary mucus of Cystic Fibrosis (CF) patients displays elevated levels of the Cathelicidin antimicrobial peptide LL-37. The interactions between the pulmonary antimicrobial peptide arsenal and Aspergillus fumigatus, a common pathogen of CF patients, have been neglected in the literature. Exposure of A. fumigatus to LL-37 and its derived fragment RK-31 (1.95 µg ml−1) for 24 h, has a stimulatory effect on growth (199.94±6.17 %, P<0.05) and (218.20±4.63 %, P<0.05) respectively, whereas scrambled (SCR)-LL-37 did not. Exposure of mycelium to 5 µg ml−1 LL-37 for 48 h increased hyphal wet weight (4.37±0.23 g, P<0.001) compared to the SCR-LL-37 treatments. The levels of Immunosuppressive metabolite gliotoxin was significantly increased at 24 h from LL-37 exposed hyphae (169.1±6.36 ng mg−1 hyphae, P<0.05) compared to the SCR-LL-37 treatments. The whole cell proteomic response A. fumigatus to LL-37 revealed an increase in proteins associated with growth (eIF-5A), tissue degradation (aspartic endopeptidase) and allergic reactions (Asp F13). By 48 h there was an increase in proteins indicative of cellular stress, growth and virulence. A. fumigatus conidia incubated in LL-37 and RK-31 displayed increased pathogenicity and fungal burden in the Galleria mellonella larvae model of aspergillosis. These results find that endogenous LL-37 paradoxically stimulates A. fumigatus growth and this may result in increased fungal growth and secretion of toxins in the lungs of CF patients.