Rhamnose-containing glycans and lipids differentially contribute to the Sporothrix-host interaction

Area of Science:

• Mycology
• Glycobiology
• Pathogen-host interactions

Background:

• Rhamnose is a key component of pathogenic Sporothrix species' cell walls, influencing host-pathogen interactions.
• The mechanisms of rhamnose incorporation into surface glycoconjugates are not fully understood.
• This study focuses on the roles of rhamnosyltransferases RHT1 and RHT2 in Sporothrix schenckii and Sporothrix brasiliensis.

Purpose of the Study:

• To investigate the functions of RHT1 and RHT2 in Sporothrix species.
• To determine how these enzymes contribute to cell wall composition, immune recognition, and virulence.
• To elucidate the species-specific roles of RHT1 and RHT2 in the pathogenicity of S. schenckii and S. brasiliensis.

Main Methods:

• Generated RHT1- and RHT2-silenced mutants in S. schenckii and S. brasiliensis.
• Assessed rhamnosyltransferase activity, cell wall composition, adhesion, and biofilm formation.
• Evaluated interactions with human immune cells (cytokine production, TLR4 recognition, phagocytosis) and virulence in Galleria mellonella.

Main Results:

• RHT1 and RHT2 silencing reduced rhamnosyltransferase activity but had distinct effects on glycoconjugates.
• RHT2 silencing affected N-linked and O-linked glycans; RHT1 silencing impacted surface glycolipids.
• Species-specific immune responses and virulence were observed, with RHT1 primarily affecting S. brasiliensis virulence and RHT2 impacting S. schenckii immune interactions.

Conclusions:

• RHT1 and RHT2 have specialized, non-redundant functions in Sporothrix rhamnosylation.
• Differential rhamnose distribution influences immune recognition, colonization, and virulence.
• These findings highlight species-specific contributions to pathogenicity in S. schenckii and S. brasiliensis.