The YeastCandida albicansBinds Complement Regulators Factor H and FHL-1

Abstract

The human facultative pathogenic yeast Candida albicans causes mucocutaneous infections and is the major cause of opportunistic fungal infections in immunocompromised patients. C. albicans activates both the alternative and classical pathway of the complement system. The aim of this study was to assay whether C. albicans binds human complement regulators in order to control complement activation at its surface. We observed binding of two central complement regulators, factor H and FHL-1, from normal human serum to C. albicans by adsorption assays, immunostaining, and fluorescence-activated cell sorter (FACS) analyses. Specificity of acquisition was further confirmed in direct binding assays with purified proteins. The surfaceattached regulators maintained their complement regulatory activities and mediated factor I-dependent cleavage of C3b. Adsorption assays with recombinant deletion mutant proteins were used to identify binding domains. Two binding sites were localized. One binding domain common to both factor H and FHL-1 is located in the N-terminal short consensus repeat domains (SCRs) 6 and 7, and the other one located in C-terminal SCRs 19 and 20 is unique to factor H. These data indicate that by surface acquisition of host complement regulators, the human pathogenic yeast C. albicans is able to regulate alternative complement activation at its surface and to inactivate toxic complement activation products.

Haemophilus influenzae Interacts with the Human Complement Inhibitor Factor H

“…In addition to inhibition of the alternative pathway, several bacteria (e.g., Moraxella catarrhalis, S. pyogenes, E. coli K1, and H. influenzae) bind C4BP and are shielded against the classical and lectin pathways (49 -51). Interestingly, many species, C. albicans, Borrelia recurrentis, and S. pyogenes, among others, have been shown to bind both FH and C4BP (26,(52)(53)(54)(55). We have recently demonstrated that non-typeable H. influenzae binds C4BP (30).…”

“…Despite the differences in FHL-1-binding, the two Hib strains 541 and 539 showed similar survival when exposed to human serum, further suggesting the importance of FH binding in serum resistance. C. albicans is another pathogen interacting with FH via two binding sites (26). The first binding domain of C. albicans is located in SCRs 6 and 7 and the second in SCRs 19 and 20.…”

Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus

“…This is in contrast to other pathways by which pathogens exploit the complement system as a means to escape the host immune response. [18][19][20][21][22][23] For example, HIV has evolved to exploit complement pathways to survive and promote transmission to permissive cells. 24 In order for systemic delivery of Ad vectors to achieve clinical practicality, a better understanding of innate immunity is needed, including how complement influences the transduction process.…”

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

“…S. aureus, Trypanosoma cruzi, and Pseudomonas aeruginosa) (17,(32)(33)(34) or indirect mechanisms by targeting and manipulating the host endogenous C3-inhibitor, Factor H (or Factor H-like proteins) (e.g. Borrelia burgdorferi, Candida albicans, and Streptococcus pyogenes) (35)(36)(37)(38). A parallel strategy employed primarily by intracellular pathogens involves membrane proteins with C3 binding capabilities that facilitate cellular internalization via the complement receptors (CR1 or CR2) (e.g.…”