The interaction of mannose binding lectin (MBL) with mannose containing glycopeptides and the resultant potential impact on invasive fungal infection

Abstract

Mannnose-binding lectin (MBL) binds oligosaccharides on the surface of microorganisms to form complexes that activate the complement cascade and facilitate phagocytosis. Teicoplanin and dalbavancin glycopeptide antibiotics possess N-acetyl glucosamine and mannose oligosaccharides that may bind MBL. Pharmaceuticals capable of binding to MBL may decrease clearance of significant pathogens such as yeast. An invasive candidemia murine model was utilized to evaluate differences in survival between mannose- and teicoplanin-treated groups compared to a control group administered normal saline. Three groups of BALB/c mice were injected with Candida albicans ATCC 44858 (1.4 x 10(6) CFU). Pharmaceutical agents were administered 2 h pre-infection and 8 h post-infection. In vivo cumulative survival at 52 h revealed 10%, 30% and 90% survival rates for mice administered mannose, teicoplanin, and saline, respectively. There was 0% survival for mice given mannose or teicoplanin at 56 h, compared with 70% for the normal saline treated mice at the same time point (P < 0.05). This in vivo study shows 'accelerated progression of infection' for Candida-inoculated mice exposed to mannose or teicoplanin compared to those given normal saline. Further, protein polyacrylamide gel electrophoresis studies suggested a potential MBL-drug interaction which may attenuate complement activation, opsonization and phagocytosis.

MBL-Mediated Opsonophagocytosis of Candida albicans by Human Neutrophils Is Coupled with Intracellular Dectin-1-Triggered ROS Production

“…MBL was well documented to have the ability to bind with high affinity to the mannose moiety of Candida species, and activate the complement system in complex with MASP, and greatly accelerate the C3/C4-mediated opsonophagocytosis of fungal pathogens [5], [6], [17], [18]. In this study, we demonstrated that the inhibitory effect on the phagocytosis of C. albicans by neutrophils caused by blockage of Dectin-1 was compensated by the exogenous MBL in a dose-dependent manner (Figure 2A–2F).…”

“…FITC-labeled C. albicans was prepared by labeling the fresh HK- C. albicans with FITC according to the methods described previously [6], [18]. The homogeneous distribution of FITC- C. albicans was confirmed by flow cytometry assay.…”

“…Furthermore, it is established that the mannan-binding lectin (MBL), a C-type or Ca 2+ -dependent lectin in the serum, has the ability to specifically recognize the mannose moiety of fungal cell wall, and greatly facilitate the C3/C4-mediated opsonophagocytosis of yeasts by neutrophils, together with MBL-associated serine proteases (MASP) [5], [6]. Therefore, the MBL is considered to be important for host resistance to hematogenously disseminated candidiasis [5], [6].…”

Interplay between Candida albicans and the Mammalian Innate Host Defense

“…The com-plement system can be activated through three pathways: the classical pathway (CP), the alternative pathway (AP), and the lectin pathway (LP). All three pathways can be activated by Candida (98,123,124). The opsonized Candida cells can be more efficiently ingested by phagocytes through the interaction between the CR3 and C3b, which is deposited on the Candida surface (62), or between the Fc receptor and the anti-Candida antibody (4).…”

Evidence of immunopathological traces in mucormycosis: an autopsy case

“…Then the hypocomplementemia might be derived from such a heavy complement activation induced by immune complex formation. Some studies report that severe fungal infection such as candidiasis can cause complement activation and vasculitis [15,16]. To our knowledge, this is the first clinical report that referred to the direct association between mucor infection and complement activation via the lectin pathway.…”