The interaction of mannose binding lectin (MBL) with mannose containing glycopeptides and the resultant potential impact on invasive fungal infection.
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.
Sealy
Patricia I
PI
University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Garner
Bianca
B
Swiatlo
Ed
E
Chapman
Stanley W
SW
Cleary
John D
JD
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D054884:Host-Pathogen Interactions; D006801:Humans; D008358:Mannose / Q000008:administration & dosage* / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D013534:Survival; D017334:Teicoplanin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D037601:Mannose-Binding Lectin; D017334:Teicoplanin; D008358:Mannose