Invention:
A new antifungal treatment is necessary, as pathogens evolve and develop immunity to current methods. Here, the inventors present calcimycin (CMN) as a novel treatment of cryptococcosis caused by Cryptococcus neoformans (Cne) and likely Cryptococcus gattii (Cga). CMN prevents the protein from continuing to splice. While the current treatment methods do not prevent intein splicing, based on a study done on mice, CMN has been shown to be effective at reducing the fungal load of cryptococcosis and may also be extended for use against other intein splicing pathogens.
Background:
Cryptococcosis is a pulmonary or disseminated infection acquired by inhalation of soil contaminated with the encapsulated yeasts Cryptococcus neoformans or C. gattii. Cryptococcus neoformans and Cryptococcus gattii affects hundreds of millions of people a year, with almost 200,000 deaths annually. In immunocompromised individuals, such as those suffering from AIDS/HIV, fungal infection is the leading cause of death. Patients who had COVID-19 are also more likely to become infected by these fungal diseases.
One strategy for treating these infections in humans is splicing on inteins from a proprotein precursor that is essential for proteins hosting inteins elements. Humans do not have a known intein splicing mechanism. Calcimycin was identified from a high throughput drug screening as having inhibitory activity against Cne and Cga. Further in vitro testing identified calcimycin as having potent intracellular inhibitory activity against Cne in macrophages. Moreover, calcimycin demonstrated inhibitory activity against intein splicing and was safe in mice while concomitantly reducing the fungal load in the lung. CMN has also been shown to be able to function in combination with amphotericin (a polyene) increasing the viability of the current treatment.
Applications:
- Anti-fungal
- Intein splicing prevention
Advantages:
- Decreased side effects
- Treats multiple fungal infections
