The study found that LL‑37, a natural antimicrobial peptide, actually makes the lung fungus Aspergillus fumigatus grow faster and produce more toxin, especially in cystic fibrosis patients. This means boosting LL‑37 isn’t a good idea if you’re worried about fungal infections.

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 <i>Aspergillus fumigatus</i>, a common pathogen of CF patients. Exposure of <i>A. fumigatus</i> to LL-37 and its derived fragment RK-31 (1.95 &#x3bc;g/ml) for 24 h had a positive effect on growth (199.94% &#xb1; 6.172% [<i>P</i> &lt; 0.05] and 218.20% &#xb1; 4.63% [<i>P</i> &lt; 0.05], respectively), whereas scrambled LL-37 peptide did not (85.12% &#xb1; 2.92%). Exposure of mycelium (preformed for 24 h) to 5 &#x3bc;g/ml intact LL-37 for 48 h increased hyphal wet weight (4.37 &#xb1; 0.23 g, <i>P</i> &lt; 0.001) compared to the control (2.67 &#xb1; 0.05 g) and scrambled LL-37 (2.23 &#xb1; 0.09 g) treatments. Gliotoxin secretion from LL-37 exposed hyphae (169.1 &#xb1; 6.36 ng/mg hyphae, <i>P</i> &lt; 0.05) was increased at 24 h compared to the results seen with the control treatment (102 &#xb1; 18.81 ng/mg hyphae) and the scrambled LL-37 treatment (96.09 &#xb1; 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 <i>A. fumigatus</i> growth and that this stimulation can result in increased fungal growth and secretion of toxins in the lungs of CF patients.