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High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
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Cryptococcus neoformans Prp8 Intein: An In Vivo Target-Based Drug Screening System in Saccharomyces cerevisiae to
José Alex Lourenço Fernandes1,2,3, Matheus da Silva Zatti1,2, Thales Domingos Arantes4
1Institute of Tropical Medicine, Federal University of Rio Grande do Norte (UFRN), Natal 59077-080, Rio Grande do Norte, Brazil.
Journal of Fungi (Basel, Switzerland)
|August 26, 2022
Summary
Researchers developed a novel drug screening system to inhibit fungal intein splicing, a potential new strategy for treating fungal infections (mycosis). This system visualizes intein splicing dynamics in vivo.
Area of Science:
- Molecular Biology
- Drug Discovery
- Mycology
Background:
- Inteins are mobile genetic elements that splice themselves out of host proteins.
- Prp8 inteins, found in fungal pathogens but not mammals, are potential therapeutic targets.
- Inhibiting intein splicing could selectively block fungal protein maturation.
Purpose of the Study:
- To develop and validate a target-based drug screening system for Prp8 intein splicing.
- To evaluate the splicing of Cryptococcus neoformans Prp8 intein (CnePrp8i) in a heterologous host.
Main Methods:
- A drug screening system was established using Saccharomyces cerevisiae expressing Ura3 as a host protein.
- The functionality of the host protein (Ura3) was preserved after intein splicing.
- Cisplatin was used to validate the system's efficacy as an intein splicing inhibitor.
Main Results:
- The heterologous system successfully demonstrated the splicing of CnePrp8i.
- Intein splicing maintained the full functionality of the non-native Ura3 host protein.
- The system allows for in vivo visualization of CnePrp8i splicing dynamics.
Conclusions:
- The developed system is effective for screening potential protein splicing inhibitors.
- This platform can facilitate the identification of new antifungal drugs targeting intein splicing.
- The system aids in understanding intein splicing mechanisms in vivo.
