Genetic diversity and molecular evolution of 3-carboxymuconate cyclase (Gp60-70), the major antigen in pathogenic...

Area of Science:

• Medical Mycology
• Molecular Evolution
• Fungal Pathogenesis

Background:

• Sporotrichosis is a neglected tropical disease caused by Sporothrix fungi, with increasing concern over virulent strains like S. brasiliensis.
• Effective control of sporotrichosis relies on rapid diagnosis and robust surveillance systems.
• Understanding the genetic diversity and evolutionary dynamics of Sporothrix species is crucial for disease management.

Purpose of the Study:

• To evaluate the 3-carboxymuconate cyclase (CMC) gene as a molecular marker for Sporothrix species.
• To analyze the genetic diversity and evolutionary patterns within pathogenic Sporothrix isolates.
• To identify potential virulence factors and targets for diagnostics and therapeutics.

Main Methods:

• Sequencing and haplotype analysis of the CMC gene from 104 Sporothrix isolates (S. brasiliensis, S. schenckii, S. globosa, S. luriei).
• Comparative analysis of CMC gene polymorphisms and chromosomal location across different species.
• Identification of conserved B-cell epitopes and N-linked glycosylation sequons within the CMC protein.

Main Results:

• The CMC gene exhibited high discriminatory power, revealing 79 unique haplotypes, surpassing traditional markers.
• Significant CMC polymorphisms in S. brasiliensis and S. schenckii suggest recent population expansion or positive selection.
• Conserved chromosomal location of CMC in pathogenic species and presence of conserved glycosylation sites indicate potential roles in virulence and adaptation.

Conclusions:

• The CMC gene is a valuable molecular marker for studying Sporothrix evolution, population dynamics, and genetic diversity.
• CMC polymorphisms and conserved features provide insights into Sporothrix pathogenicity and adaptation.
• This research aids in developing improved diagnostics and therapeutics for sporotrichosis control.