The yeast Candida albicans binds complement regulators factor H and FHL-1

Area of Science:

• Immunology
• Mycology
• Microbiology

Background:

• Candida albicans is a major opportunistic fungal pathogen causing infections in immunocompromised individuals.
• C. albicans can activate both the alternative and classical complement pathways, key components of the innate immune system.
• Understanding how C. albicans evades the host immune response is crucial for developing effective treatments.

Purpose of the Study:

• To investigate whether Candida albicans binds human complement regulators to control complement activation.
• To identify the specific complement regulators C. albicans acquires from human serum.
• To determine the functional consequences of regulator binding for C. albicans survival.

Main Methods:

• Adsorption assays, immunostaining, and fluorescence-activated cell sorter (FACS) analyses were used to detect regulator binding.
• Direct binding assays with purified proteins confirmed the specificity of acquisition.
• Recombinant deletion mutant proteins were employed to map the binding domains of the regulators on C. albicans.

Main Results:

• Candida albicans was found to bind the complement regulators factor H and FHL-1 from normal human serum.
• Surface-bound regulators retained their activity, mediating factor I-dependent cleavage of C3b.
• Two binding sites were identified: one common to factor H and FHL-1 (SCRs 6 and 7) and another unique to factor H (SCRs 19 and 20).

Conclusions:

• Candida albicans actively acquires host complement regulators, specifically factor H and FHL-1, onto its surface.
• This acquisition allows C. albicans to regulate complement activation, particularly the alternative pathway, at its surface.
• By controlling complement deposition and activation, C. albicans can evade immune attack and inactivate toxic complement products, contributing to its pathogenicity.