Mucoricin
Mucoricin is a protein toxin produced by fungi in the order Mucorales, the fungi that cause mucormycosis. It is a virulence factor that damages host tissues and interferes with the immune response during infection. The toxin has been most extensively studied in Rhizopus delemar.[1][2] Mucoricin was named for its similarities to the plant toxin ricin, sharing structural features with the ricin B chain and the ability of the ricin A chain to inhibit host protein synthesis.[3]
Structure and activity
[edit]Mucoricin is a 17 kDa protein encoded by the RLT1 (ricin-like toxin 1) gene in R. delemar. It has structural and functional similarities to the plant toxin ricin. Unlike ricin, which consists of separate A and B chains, mucoricin is a single protein. Mucoricin has strong structural similarity to the lectin-binding B chain of ricin, which allows ricin to bind to sugars on the surface of host cells. It also has activity similar to the ricin A chain, which inhibits protein synthesis by inactivating ribosomes.[1]
Role in mucormycosis
[edit]Mucoricin contributes to the tissue damage and vascular dysfunction associated with mucormycosis. In mice, administration of purified mucoricin induced inflammation, hemorrhage, and tissue necrosis, while suppression of RLT1 in R. delemar reduced virulence.[1]
Mucoricin is primarily associated with the hyphal stage of growth. While heat-killed fungal hyphae showed reduced activity, the resulting cytopathic damage to host cells is still significant, suggesting that the toxin is largely heat-stable.[1] Additionally, purified mucoricin can also independently cause cellular damage.
Mucoricin also contributes to the interaction between Mucorales fungi and neutrophils, white blood cells that play an important role in controlling fungal infections.[4] Normally, fungal germination triggers neutrophils to cluster at the site of infection. CR3 receptors on neutrophils recognize β-glucan residues found on the surface of fungi, inducing neutrophil release of reactive oxygen species (ROS) to control the fungal infection. Mucoricin released by Mucorales fungi selectively bind to β-glucan on the surface of the fungi, concentrating the toxin around the fungus, where it promotes neutrophil apoptosis and inhibits neutrophil swarming.[4]
Potential therapeutic target
[edit]Mucoricin has been investigated as a potential therapeutic target for mucormycosis. Antibodies against the toxin have been shown to reduce cellular damage and vascular permeability.[citation needed] In silico analysis has identified several potential compounds that may selectively inhibit the toxin.[5]
References
[edit]- 1 2 3 4 Soliman, Sameh S. M.; Baldin, Clara; Gu, Yiyou; Singh, Shakti; Gebremariam, Teclegiorgis; Swidergall, Marc; Alqarihi, Abdullah; Youssef, Eman G.; Alkhazraji, Sondus; Pikoulas, Antonis; Perske, Christina; Venkataramani, Vivek; Rich, Abigail; Bruno, Vincent M.; Hotopp, Julie Dunning (2021). "Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis". Nature Microbiology. 6 (3): 313–326. doi:10.1038/s41564-020-00837-0. ISSN 2058-5276. PMC 7914224. PMID 33462434.
- ↑ Papon, Nicolas; Naglik, Julian R.; Hube, Bernhard; Goldman, Gustavo H. (2021-04-26). "Fungal pathogenesis: A new venom". Current Biology. 31 (8). Elsevier: R391–R394. Bibcode:2021CBio...31.R391P. doi:10.1016/j.cub.2021.03.015. ISSN 0960-9822. PMID 33905698.
- ↑ Alqarihi, Abdullah; Kontoyiannis, Dimitrios P.; Ibrahim, Ashraf S. (2023). "Mucormycosis in 2023: an update on pathogenesis and management". Frontiers in Cellular and Infection Microbiology. 13 1254919. doi:10.3389/fcimb.2023.1254919. ISSN 2235-2988. PMC 10552646. PMID 37808914.
- 1 2 Baimpa, Stavroula; Sertedakis, Matthaios; Drakos, Elias; Akoumianaki, Tonia; Vatikioti, Alexandra; Gu, Yiyou; Dolati, Sanam; Koutsopoulos, Anastasios; Ibrahim, Ashraf S. (2025-10-29), "Mucoricin binding to β-glucan sites on germinating Mucorales spores disrupts neutrophil swarming to promote pathogenicity", bioRxiv : The Preprint Server for Biology, doi:10.1101/2025.10.28.685056, PMC 12636483, PMID 41279284, 2025.10.28.685056
- ↑ Madanagopal, Premnath; Ramprabhu, Nagarjun; Jagadeesan, Rahul (2022-01-31). "In silico prediction and structure-based multitargeted molecular docking analysis of selected bioactive compounds against mucormycosis". Bulletin of the National Research Centre. 46 (1): 24. doi:10.1186/s42269-022-00704-4. ISSN 2522-8307. PMC 8802264. PMID 35125861.
