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Effect of Anti-Glycosphingolipid Monoclonal Antibodies in Pathogenic Fungal Growth and Differentiation. Characterization of Monoclonal Antibody MEST-3 Directed to Manpα1→3Manpα1→2IPC

Summary

This research investigated how antibodies targeting specific sugar-containing lipids on fungal surfaces can prevent fungal growth and transformation between different forms. The findings suggest these lipids play crucial roles in fungal survival and could be targeted for new antifungal treatments. Impact on everyday life: – Could lead to new treatments for serious fungal infections – Provides better understanding of how fungi cause disease – May help develop better diagnostic tests for fungal infections – Could benefit immunocompromised patients at risk for fungal infections – Demonstrates potential for antibody-based therapies against fungi

Background

Studies from the 1990s demonstrated the presence of fungal glycoinositol phosphorylceramides (GIPCs) with unique structures, some showing reactivity with sera from patients with histoplasmosis, paracoccidioidomycosis or aspergillosis. Fungal GIPCs were found to inhibit T lymphocyte proliferation in vitro, and studies showed many fungi species are vulnerable to inhibitors of sphingolipid biosynthesis.

Objective

To characterize a new monoclonal antibody (MEST-3) directed to fungal glycosphingolipids and evaluate its effects along with other anti-glycosphingolipid antibodies on fungal growth and differentiation.

Results

MEST-3 specifically recognized the epitope Manpα1→3Manpα1→2Ins present in several pathogenic fungi. Both MEST-1 and MEST-3 showed significant inhibition of fungal growth and yeast-to-mycelium differentiation in a dose-dependent manner. MEST-3 inhibited growth and differentiation in all three fungi tested, while MEST-1 only affected P. brasiliensis and H. capsulatum. MEST-2, directed to glucosylceramide, showed no significant inhibitory effects.

Conclusion

Monoclonal antibodies directed to specific glycosphingolipids can interfere with fungal growth and differentiation. The results suggest that proper organization of surface glycosphingolipids in fungi may be essential for various processes including growth, morphological transition and infectivity. These molecules could represent potential targets for new therapeutic approaches based on protective antibodies.
  • Published in:BMC Microbiology,
  • Study Type:Laboratory Research,
  • Source: 10.1186/1471-2180-10-47
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