Abstract
Antimicrobial peptides and proteins (AMPs) provide an important line of defence against invading microorganisms. However, the activity of AMPs against the human fungal pathogen Aspergillus fumigatus remains poorly understood. Therefore, the aim of this study was to characterise the anti-Aspergillus activity of specific human AMPs, and to determine whether A. fumigatus can possess resistance to specific AMPs, as a result of in-host adaptation. AMPs were tested against a wide range of clinical isolates of various origins (including cystic fibrosis patients, as well as patients with chronic and acute aspergillosis). We also tested a series of isogenic A. fumigatus isolates obtained from a single patient over a period of 2 years. A range of environmental isolates, obtained from soil in Scotland, was also included. Firstly, the activity of specific peptides was assessed against hyphae using a measure of fungal metabolic activity. Secondly, the activity of specific peptides was assessed against germinating conidia, using imaging flow cytometry as a measure of hyphal growth. We showed that lysozyme and histones inhibited hyphal metabolic activity in all the A. fumigatus isolates tested in a dose-dependent fashion. In addition, imaging flow cytometry revealed that histones, β-defensin-1 and lactoferrin inhibited the germination of A. fumigatus conidia.
Highlights
The human opportunistic fungal pathogen Aspergillus fumigatus is the main causative agent of pulmonary aspergillosis, which ranges from allergic syndromes and chronic infections to life-threatening invasive aspergillosis [1]
Incubation with 5–160 μM lysozyme resulted in concentration-dependent decreases in the metabolic activity of A. fumigatus hyphae
Incubation with 5–50 μM LL-37, 10–40 μM lactoferrin or 1–10 μM β-defensin-1 did not result in reduced metabolic activity of hyphae in any isolates tested
Summary
The human opportunistic fungal pathogen Aspergillus fumigatus is the main causative agent of pulmonary aspergillosis, which ranges from allergic syndromes and chronic infections to life-threatening invasive aspergillosis [1]. A. fumigatus encounters various stresses in-host during infection or colonisation. The fungus must adapt to withstand these stresses [2,3]. These stresses include exogenous stresses, such as azole antifungals, and endogenous stresses that include oxidative stress, nutrient depletion and antimicrobial peptides and proteins (AMPs) [2,3]. Over 100 human AMPs have been described, ranging in size from 10 to 149 amino acids, and have net charges
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