Author:
EJ Côté1,2*, A Classen3#, E Marcolefas4, J Ronholm3, DC Sheppard1,2, L Whyte4, F Le Mauff1,2
Author address:
1Department of Microbiology and Immunology , McGill University, Montreal, Canada
2Infectious Diseases and Immunity in Global Heath Program, Research Institute of the McGill University Health Center, Montreal, Canada
3Department of Food Science and Agricultural Chemistry, McGill University, Montreal, Canada
4Department of Natural Resources Sciences, McGill University, Montreal, Canada
#Current address: Health Canada, Ottawa, Ontario, Canada
Full conference title:
10th Advances Against Aspergillosis and Mucormycosis
Date: 2 February 2022
Abstract:
Background:
The alarming rise in the rate of invasive fungal infections and the emergence of resistance to commonly available antifungals has highlighted the urgent need for new antifungal agents. One approach to the discovery of such novel agents is to mine the biodiversity of unexplored microbial ecosystems. Screening of microbial isolates from a recent expedition by our group to the Axel Heiberg Island, Nunavut in the Canadian Arctic identified a novel Streptomyces species that exhibited antifungal activity.
Methods:
The antifungal activity of extracts from the arctic Streptomyces against a panel of human fungal pathogens, including mucormycetes and azole-resistant clinical isolates of Aspergillus fumigatus, was assessed using CLSI methods. The active molecule, termed Stradam, was purified by chromatography/mass spectrometry. Stradam cytotoxicity was evaluated using several cell lines, and its effects on fungal morphogenesis were examined by confocal microscopy.
Results:
Organic extracts from the Arctic Streptomyces showed a broad range of activity affecting all fungal species tested, including the resistant clinical strains. However, growth of Aspergillus fumigatus and Rhizopus oryzae were the most strongly inhibited. Confocal microscopy revealed that the germination of these species was arrested after the swelling of the spores, preventing their development into germlings. Fractionation and purification studies of the raw extract revealed that the antifungal activity of these preparations was due to the presence of a single active compound with a m/z ratio of 467. Semi-purified molecule of Stradam was not cytotoxic to the A549 epithelial cell line and did not induce red blood cell lysis at concentrations well above those required for the inhibition of fungal growth.
Conclusion:
Our studies have identified a potential novel antifungal agent with activity against R. oryzae and azole-resistant strains of A. fumigatus. Further studies to define the structure of this molecule, and its potential mechanism of action are ongoing.
Abstract Number: 62
Conference Year: 2022
Link to conference website: https://aaam2022.org/
URL Conference abstract: