Blachowicz, Adriana and Raffa, Nicholas and Bok, Jin Woo and Choera, Tsokyi and Knox, Benjamin and Lim, Fang Yun and Huttenlocher, Anna and Wang, Clay C. C. and Venkateswaran, Kasthuri and Keller, Nancy P. (2020) Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different Aspergillus fumigatus Strains. mBio, 11 (1). Art. No. e03415-19. ISSN 2150-7511. PMCID PMC7029147. doi:10.1128/mbio.03415-19. https://resolver.caltech.edu/CaltechAUTHORS:20200218-110838174
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Abstract
Fungi are versatile organisms which thrive in hostile environments, including the International Space Station (ISS). Several isolates of the human pathogen Aspergillus fumigatus have been found contaminating the ISS, an environment with increased exposure to UV radiation. Secondary metabolites (SMs) in spores, such as melanins, have been shown to protect spores from UV radiation in other fungi. To test the hypothesis that melanin and other known spore SMs provide UV protection to A. fumigatus isolates, we subjected SM spore mutants to UV-C radiation. We found that 1,8-dihydroxynaphthalene (DHN)-melanin mutants of two clinical A. fumigatus strains (Af293 and CEA17) but not an ISS-isolated strain (IF1SW-F4) were more sensitive to UV-C than their respective wild-type (WT) strains. Because DHN-melanin has been shown to shield A. fumigatus from the host immune system, we examined all DHN mutants for virulence in the zebrafish model of invasive aspergillosis. Following recent studies highlighting the pathogenic variability of different A. fumigatus isolates, we found DHN-melanin to be a virulence factor in CEA17 and IF1SW-F4 but not Af293. Three additional spore metabolites were examined in Af293, where fumiquinazoline also showed UV-C-protective properties, but two other spore metabolites, monomethylsulochrin and fumigaclavine, provided no UV-C-protective properties. Virulence tests of these three SM spore mutants indicated a slight increase in virulence of the monomethylsulochrin deletion strain. Taken together, this work suggests differential roles of specific spore metabolites across Aspergillus isolates and by types of environmental stress.
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| Additional Information: | © 2020 Blachowicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Received 29 December 2019; Accepted 8 January 2020; Published 18 February 2020. Part of the research described in this publication was carried out at the Jet Propulsion Laboratory (JPL), California Institute of Technology, under a contract with the National Aeronautics and Space Administration (NASA). This research was funded by NASA’s Space Biology grant NNH16ZTT001N NRA awarded to N.P.K. and funded student fellowships to A.B. and N.R. We thank Bangyan L. Stiles for enabling the Hoefer UV-C crosslinker to conduct the UV-C exposure experiment. A.B. drafted the manuscript, conducted UV-C experiments, and contributed to data analysis and interpretation. N.R. drafted parts of the manuscript and performed in vivo virulence assays. F.Y.L. helped with the experimental design of UV-C testing and created several genetically transformed strains. J.W.B., T.C., and B.K. created the genetically modified strains used in the study. A.H. provided reagents and aided experimental design of the zebrafish virulence testing. N.P.K., C.C.C.W., and K.V. formulated the concept of the study and were involved in experiment execution and manuscript drafting. All authors read and approved the final manuscript. We declare no competing interests. | ||||||||||||||||||
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| Issue or Number: | 1 | ||||||||||||||||||
| PubMed Central ID: | PMC7029147 | ||||||||||||||||||
| DOI: | 10.1128/mbio.03415-19 | ||||||||||||||||||
| Record Number: | CaltechAUTHORS:20200218-110838174 | ||||||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20200218-110838174 | ||||||||||||||||||
| Official Citation: | Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different Aspergillus fumigatus Strains. Adriana Blachowicz, Nicholas Raffa, Jin Woo Bok, Tsokyi Choera, Benjamin Knox, Fang Yun Lim, Anna Huttenlocher, Clay C. C. Wang, Kasthuri Venkateswaran, Nancy P. Keller. mBio Feb 2020, 11 (1) e03415-19; DOI: 10.1128/mBio.03415-19 | ||||||||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||
| ID Code: | 101323 | ||||||||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||||||||
| Deposited By: | Tony Diaz | ||||||||||||||||||
| Deposited On: | 18 Feb 2020 20:05 | ||||||||||||||||||
| Last Modified: | 16 Nov 2021 18:01 |
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