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Allelopathic compound 2-methoxy-1,4-naphthoquinone is broadly effective against pathogenic Prototheca species in
Amir Aliramezani1, Grzegorz Szewczyk2, Krystian Mokrzyński2
1Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Abstract:
Unpigmented, yeast-like Prototheca algae are emerging pathogens responsible for unusual infections in humans and animals. Their treatment is often unsuccessful, as traditional antifungals and antibacterials show unsatisfactory activity against Prototheca. Therefore, the development of improved drugs that consider the peculiarities of algal biology is needed. Here, we describe a novel anti-Prototheca compound, the 2-methoxy-1,4-naphthoquinone, identified among molecules known to mediate plant and algal allelopathy. The 2-methoxy-1,4-naphthoquinone was highly active in vitro against a range of Prototheca isolates from different species, both planktonically and in biofilms. Its mode of action included the induction of toxic reactive oxygen species, and it targeted energy generation in the pathogen's mitochondria. It effectively treated Prototheca bovis skin infection in a mouse model, demonstrating translational potential. Altogether, this study not only identified a new effective anti-Prototheca compound, but also identified 1,4-naphthoquinone backbone as a lead structure for further therapeutic development and demonstrated the feasibility of exploring known anti-plant compounds as a source of anti-Prototheca treatments.
Insights
A novel compound, 2-methoxy-1,4-naphthoquinone, shows high activity against the emerging pathogen Prototheca. This naphthoquinone derivative effectively treats Prototheca infections and offers a promising lead for new drug development.
Area of Science:
- Microbiology
- Mycology
- Drug Discovery
Background:
- Prototheca algae are emerging pathogens causing difficult-to-treat infections in humans and animals.
- Existing antifungal and antibacterial treatments are largely ineffective against Prototheca due to its unique biology.
Purpose of the Study:
- To identify and characterize novel therapeutic agents effective against Prototheca.
- To explore the potential of plant and algal allelopathic compounds as anti-Prototheca agents.
Main Methods:
- Screening of allelopathic compounds for anti-Prototheca activity.
- In vitro testing against various Prototheca isolates (planktonic and biofilm).
- In vivo efficacy testing using a mouse model of Prototheca bovis skin infection.
Main Results:
- 2-methoxy-1,4-naphthoquinone demonstrated potent in vitro activity against diverse Prototheca species.
- The compound induced reactive oxygen species and targeted mitochondrial energy production.
- Successful treatment of Prototheca bovis skin infection in a mouse model was achieved.
Conclusions:
- 2-methoxy-1,4-naphthoquinone is a novel and effective anti-Prototheca compound.
- The 1,4-naphthoquinone scaffold represents a promising lead for developing new treatments for Prototheca infections.
- Allelopathic compounds are a viable source for discovering novel anti-Prototheca therapeutics.
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