Abstract Number: PB1790
Meeting: ISTH 2020 Congress
Background: Candida albicans is an opportunistic pathogen that causes a wide variety of infections, including life-threatening systemic candidiasis. The virulence of this pathogen includes their ability to form hyphae and biofilms, protecting it from the host immune system and antifungal drugs. The surface of C. albicans is rich in O-mannan which, along with the hyphal protein Als3p, has been shown to be crucial for biofilm formation. There is evidence to suggest that haemostatic proteins participate in biofilm formation. Factor XII (FXII) is a contact pathway protein which when activated can initiate coagulation, fibrinolysis and inflammation, however its role in biofilm formation is currently unclear.
Aims: Here we investigate the interaction between FXII and C. albicans to define whether the contact pathway influences virulence and biofilm formation.
Methods: Binding of FXII to C. albicans wild-type (WT), als3Δ/als3Δ and O-mannan mnt1Δ/mnt2Δ mutants was analysed by confocal microscopy with Dylight488/550-FXII(a). C. albicans biofilms were formed over 48 h on polymer squares ± FXII and quantified by colony forming units/ml.
Results: We have demonstrated that FXII and its activated form, FXIIa, bind to WT hyphae, but not yeast cells. Binding was not dependent on the presence of zinc. In marked contrast, FXII bound only to the germinating hyphal tip of the als3Δ/als3Δ mutant and did not bind mnt1Δ/mnt2Δ, implicating Als3p and O-mannan in the interaction of FXII with C. albicans. Our data show that biofilm formation is increased in the presence of purified FXII, and conversely is decreased in FXII-deficient plasma relative to normal plasma.
Conclusions: Our data show clear binding of FXII to the C. albicans hyphae. Use of mutant forms indicate potential roles for Als3p and O-mannosylated glycans in the interaction of FXII with C. albicans. Our studies indicate that FXII-hyphae binding promotes biofilm formation, thereby implicating this haemostatic protein in the virulence of this fungal pathogen.
To cite this abstract in AMA style:Williams ML, Childers DS, Brand AC, Mutch NJ. Coagulation Factor XII Binds to the Opportunistic Pathogen, Candida albicans and Promotes Biofilm Formation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/coagulation-factor-xii-binds-to-the-opportunistic-pathogen-candida-albicans-and-promotes-biofilm-formation/. Accessed August 15, 2022.
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