| Full text | |
| Author(s): |
de Almeida, Otavio Guilherme Goncalves
;
Kress, Marcia Regina von Zeska
Total Authors: 2
|
| Document type: | Journal article |
| Source: | MICROORGANISMS; v. 12, n. 8, p. 17-pg., 2024-08-01. |
| Abstract | |
Fungal resistance is a public health concern due to the limited availability of antifungal resources and the complexities associated with treating persistent fungal infections. Azoles are thus far the primary line of defense against fungi. Specifically, azoles inhibit the conversion of lanosterol to ergosterol, producing defective sterols and impairing fluidity in fungal plasmatic membranes. Studies on azole resistance have emphasized specific point mutations in CYP51/ERG11 proteins linked to resistance. Although very insightful, the traditional approach to studying azole resistance is time-consuming and prone to errors during meticulous alignment evaluation. It relies on a reference-based method using a specific protein sequence obtained from a wild-type (WT) phenotype. Therefore, this study introduces a machine learning (ML)-based approach utilizing molecular descriptors representing the physiochemical attributes of CYP51/ERG11 protein isoforms. This approach aims to unravel hidden patterns associated with azole resistance. The results highlight that descriptors related to amino acid composition and their combination of hydrophobicity and hydrophilicity effectively explain the slight differences between the resistant non-wild-type (NWT) and WT (nonresistant) protein sequences. This study underscores the potential of ML to unravel nuanced patterns in CYP51/ERG11 sequences, providing valuable molecular signatures that could inform future endeavors in drug development and computational screening of resistant and nonresistant fungal lineages. (AU) | |
| FAPESP's process: | 22/00754-4 - Genomic analysis of clinical isolates of Fusarium spp. and genetic determinants of azole resistance using machine learning methods |
| Grantee: | Otávio Guilherme Gonçalves de Almeida |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/07546-2 - Resistance study of Fusarium spp. clinical isolates to amphotericin B and azoles |
| Grantee: | Marcia Regina von Zeska Kress |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 23/12463-7 - Study of the resistance of Fusarium and Aspergillus clinical isolates to azole antifungals and the biosynthesis of metallic nanoparticles as an antifungal therapeutic alternative. |
| Grantee: | Marcia Regina von Zeska Kress |
| Support Opportunities: | Regular Research Grants |