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Published on: June 21, 2018
Genotypic and Phenotypic Diversity of Cryptococcus gattii VGII Clinical Isolates and Its Impact on Virulence
Vanessa A Barcellos1, Liline M S Martins2,3, Alide C L Fontes4
1Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Abstract:
The Cryptococcus gattii species complex harbors the main etiological agents of cryptococcosis in immunocompetent patients. C. gattii molecular type VGII predominates in the north and northeastern regions of Brazil, leading to high morbidity and mortality rates. C. gattii VGII isolates have a strong clinical relevance and phenotypic variations. These phenotypic variations among C. gattii species complex isolates suggest that some strains are more virulent than others, but little information is available related to the pathogenic properties of those strains. In this study, we analyzed some virulence determinants of C. gattii VGII strains (CG01, CG02, and CG03) isolated from patients in the state of Piauí, Brazil. The C. gattii R265 VGIIa strain, which was isolated from the Vancouver outbreak, differed from C. gattii CG01, CG02 and CG03 isolates (also classified as VGII) when analyzed the capsular dimensions, melanin production, urease activity, as well as the glucuronoxylomannan (GXM) secretion. Those differences directly reflected in their virulence potential. In addition, CG02 displayed higher virulence compared to R265 (VGIIa) strain in a cryptococcal murine model of infection. Lastly, we examined the genotypic diversity of these strains through Multilocus Sequence Type (MLST) and one new subtype was described for the CG02 isolate. This study confirms the presence and the phenotypic and genotypic diversity of highly virulent strains in the Northeast region of Brazil.
Insights
Highly virulent Cryptococcus gattii VGII strains are prevalent in Northeast Brazil, exhibiting significant phenotypic and genotypic diversity. These strains show varied virulence, with CG02 demonstrating increased pathogenicity in a murine model.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Biology
Background:
- Cryptococcus gattii species complex causes cryptococcosis, particularly in immunocompetent individuals.
- Molecular type VGII of C. gattii is dominant in Northeast Brazil, associated with severe disease.
- Phenotypic variations among C. gattii isolates suggest differences in virulence, but pathogenic properties remain understudied.
Purpose of the Study:
- To investigate virulence determinants and genotypic diversity of C. gattii VGII strains from Piauí, Brazil.
- To compare the virulence potential of Brazilian C. gattii VGII isolates with a reference strain.
Main Methods:
- Analysis of capsular dimensions, melanin production, urease activity, and glucuronoxylomannan (GXM) secretion.
- Virulence assessment using a murine model of cryptococcosis.
- Genotypic characterization via Multilocus Sequence Typing (MLST).
Main Results:
- Brazilian C. gattii VGII isolates (CG01, CG02, CG03) exhibited distinct phenotypic characteristics compared to the R265 VGIIa reference strain.
- The CG02 isolate demonstrated higher virulence than the R265 strain in the murine model.
- MLST analysis revealed genotypic diversity, including a novel subtype for the CG02 isolate.
Conclusions:
- Northeast Brazil harbors phenotypically and genotypically diverse C. gattii VGII strains.
- These strains possess significant virulence potential, contributing to cryptococcosis morbidity and mortality.
- Further research into the pathogenic mechanisms of these strains is warranted.
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