Activities per year
Of the few antifungal agents available for the treatment of mycosis, only the amphotericin B deoxycholate and fluconazole are available in developing countries to treat cryptococcal infections. While amphotericin is used together with fluconazole in induction therapy, fluconazole is used as the sole medication in consolidation and maintenance therapies, and is also recommended as primary prophylaxis for cryptococcosis. In developed countries, however, 5-fluorocytocin is used instead of fluconazole in induction therapy because of its higher efficacy.
Although antifungal resistance in C. neoformans and C. gattii is generally rare, in Colombia not only clinical but also environmental isolates resistant to fluconazole have been reported, which has been associated with therapeutic failures and relapses. In these two Cryptococcus species, resistance to azoles such as fluconazole is associated with the molecular mechanism of point mutations in the ERG11 gene, which encodes an enzyme that converts lanosterol into ergosterol, the target of action of azole compounds. In addition, the phenotypic phenomenon of intrinsic heteroresistance to fluconazole has been described, which is characterized by the ability of the fungus to adapt to high concentrations of the antifungal gradually.
Because the decreased susceptibility or resistance of C. neoformans and C. gattii to fluconazole influences the management of cryptococcosis and worsens the prognosis, it is important to know the mechanisms of the origin of such resistance, which in turn could lead to define methodologies that improve the diagnosis of resistant isolates and direct therapeutic strategies, making them more appropriate and timely.
1. Identification and inventory of ERG11 gene polymorphisms associated with fluconazole resistance in Colombian clinical and environmental isolates of C. neoformans and C. gattii.
2. Creation of a database with the microbiological and molecular information of the C. neoformans and C. gattii isolates included in the study, as well as a collection of their DNA.
3. Standardization of methodologies for the amplification and sequencing of the ERG11 gene and for the evaluation of fluconazole heteroresistance of C. neoformans and C. gattii.
4. Contribution with the collection of nucleotide sequences of public access for the study of pathogens of importance in Public Health, such as C. neoformans and C. gattii, through the deposit of the sequences obtained in the GenBank databases.
5. Preparation of a manuscript for publication in an international indexed journal.
6. Participation and presentation of study results at a national or international scientific event
Expected training products:
1.Articulation of a young researcher in the project
|Effective start/end date||3/13/20 → 12/2/22|
UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):
Main Funding Source
- Competitive Funds
- 2 Participation in conference
Carolina Firacative (Participant)Nov 24 2021 → Nov 26 2021
Activity: Participation or organization of an event › Participation in conference