Inactivation of the Complement Lectin Pathway by Candida tropicalis Secreted Aspartyl Protease-1

Area of Science:

• Mycology
• Immunology
• Biochemistry

Background:

• Candida tropicalis is an opportunistic fungal pathogen causing infections, especially in immunocompromised individuals.
• Antifungal drug resistance is a growing concern, necessitating new therapeutic strategies.
• Understanding C. tropicalis immune evasion mechanisms is crucial for developing novel antifungal therapies.

Purpose of the Study:

• To investigate the immune evasion properties of C. tropicalis secreted aspartic protease 1 (Sapt1).
• To determine if Sapt1 can degrade components of the host immune system, specifically the complement system.

Main Methods:

• Recombinant Sapt1 production using a Kluyveromyces lactis yeast expression system.
• Screening of Sapt1 for proteolytic activity against human complement proteins and immunoglobulins.
• Analysis of Sapt1 gene expression in clinical isolates using RT-qPCR.

Main Results:

• Sapt1 efficiently cleaved human mannose-binding lectin (MBL) and collectin-11, key initiators of the lectin complement pathway.
• Sapt1 also cleaved DC-SIGN on dendritic cells, but not other complement proteins like C1q, C3, or immunoglobulins.
• Proteolytic activity was optimal under acidic conditions (pH 5.2).
• Sapt1 prevented lectin pathway activation and was secreted by clinical C. tropicalis isolates, with higher Sapt1 gene expression compared to a reference strain.

Conclusions:

• C. tropicalis utilizes Sapt1 to target and inhibit the lectin complement pathway, a critical host defense mechanism.
• Sapt1's ability to degrade MBL and collectin-11 highlights its role in immune evasion and pathogenesis.
• Sapt1 represents a potential therapeutic target for combating C. tropicalis infections.