| Full text | |
| Author(s): |
Calvete, Crislaine Lambiase
[1, 2]
;
Martho, Kevin Felipe
[1]
;
Felizardo, Gabrielle
[1]
;
Paes, Alexandre
[1]
;
Nunes, Joao Miguel
[1]
;
Ferreira, Camila Oliveira
[1]
;
Vallim, Marcelo A.
[1]
;
Pascon, Renata C.
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Fed Sao Paulo, Dept Biol Sci, Campus Diadema, Diadema, SP - Brazil
[2] Univ Sao Paulo, Biotechnol Grad Program, Sao Paulo, SP - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | PLoS One; v. 14, n. 1 JAN 25 2019. |
| Web of Science Citations: | 4 |
| Abstract | |
Cryptococcosis is an Invasive Fungal Infection (IFI) caused by Cryptococcus neoformans, mainly in immunocompromised patients. Therapeutic failure due to pathogen drug resistance, treatment inconstancy and few antifungal options is a problem. The study of amino acid biosynthesis and uptake represents an opportunity to explore possible development of novel antifungals. C. neoformans has 10 amino acids permeases, two of them (Aap3 and Aap7) not expressed at the conditions tested, and five were studied previously (Aap2, Aap4, Aap5, Mup1 and Mup3). Our previous results showed that Aap4 and Aap5 are major permeases with overlapping functions. The aap4 Delta/aap5 Delta double mutant fails to grow in amino acids as sole nitrogen source and is avirulent in animal model. Here, we deleted the remaining amino acid permeases (AAP1, AAP6, AAP8) that showed gene expression modulation by nutritional condition and created a double mutant (aap1 Delta/aap2 Delta). We studied the virulence attributes of these mutants and explored the regulatory mechanism behind amino acid uptake in C. neoformans. The aap1 Delta/aap2 Delta strain had reduced growth at 37 degrees C in L-amino acids, reduced capsule production and was hypovirulent in the Galleria mellonella animal model. Our data, along with previous studies, (i) complement the analysis for all 10 amino acid permeases mutants, (ii) corroborate the idea that these transporters behave as global permeases, (iii) are required during heat and nutritional stress, and (iv) are important for virulence. Our study also indicates a new possible link between Ras1 signaling and amino acids uptake. (AU) | |
| FAPESP's process: | 16/14542-8 - Genetic characterization of the regulatory elements of the biosynthesis and uptake of amino acids and their role in virulence of Cryptococcus neoformans. |
| Grantee: | Renata Castiglioni Pascon |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/23890-0 - Identification of molecular targets in Cryptococcus neoformans and the importance of AAP1 amino acid permease for virulence factors |
| Grantee: | João Miguel Alves Nunes |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 15/04400-9 - The role of autophagy in Cryptococcus neorformas high temperature (37°C) growth and virulence |
| Grantee: | Marcelo Afonso Vallim |
| Support Opportunities: | Regular Research Grants |