Silencing of mitochondrial alternative oxidase gene of Aspergillus fumigatus enhances reactive oxygen species production and killing of the fungus by macrophages
Abstract
We previously demonstrated that conidia from Aspergillus fumigatus incubated with menadione and paraquat increases activity and expression of cyanide-insensitive alternative oxidase (AOX). Here, we employed the RNA silencing technique in A. fumigatus using the vector pALB1/aoxAf in order to down-regulate the aox gene. Positive transformants for aox gene silencing of A. fumigatus were more susceptible both to an imposed in vitro oxidative stress condition and to macrophages killing, suggesting that AOX is required for the A. fumigatus pathogenicity, mainly for the survival of the fungus conidia during host infection and resistance to reactive oxygen species generated by macrophages.
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The importance of AOX in morphogenesis and resistance to oxidative stress has been demonstrated in A. fumigatus, C. neoformans and P. brasiliensis.
“The importance of AOX in morphogenesis and resistance to oxidative stress has been demonstrated in several fungal pathogens, including A. fumigatus (Magnani et al. 2008), C. neoformans (Akhter et al. 2003) and Paracoccidioides brasiliensis (Martins et al. 2011).”
From The potential of respiration inhibition as a new approach to combat human fungal pathogens (2019) · cites this paper as Magnani et al. 2008
The effect of increased ROS and dead cells may have clinical relevance because oxidative stress reduces microbial pathogenicity by enhanced killing by macrophages.
“Overall, this is an effect that may have clinical relevance because it is known that oxidative stress reduces microbial pathogenicity by enhanced killing by macrophages [35], as shown for A. fumigatus [36].”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [36]
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References 31 · Cited by 58
- Authors
- Magnani, T., Soriani, F. M., Martins, V. D. P., Policarpo, A. C. D. F., Sorgi, C. A., Faccioli, L. H., Curti, C., & Uyemura, S. A.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Uyemura, Sérgio Akira
- ORCID
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2008-12
- Volume
- 40
- Issue
- 6
- Pages
- 631-636
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W2059774589
- Cited by
- 58
- References
- 31
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Aspergillus fumigatus, alternative oxidase, reactive oxygen species, macrophage killing, oxidative stress, fungal pathogenicity, host-pathogen interaction, RNA interference
- MeSH terms
- Alternative Oxidase, Aspergillus fumigatus, Cells, Cultured, Humans, Macrophages, Mitochondria, Oxidoreductases, Plant Proteins, Spores, Fungal, Apoptosis, Reactive Oxygen Species, Gene Silencing, Mitochondrial Proteins
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