ArticleThe Journal of clinical investigation2014
CotH3 mediates fungal invasion of host cells during mucormycosis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 2 of them syntheses that pooled it.
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Who cites it
162 citing papers in PubMed, 2 syntheses or guidelines pooled it, 246 citations in OpenAlex.
- Mucormycosis in Paediatric Patients After Haematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.Mycoses · 2025Pooled it
- Epidemiology and Pathophysiology of COVID-19-Associated Mucormycosis: India Versus the Rest of the World.Mycopathologia · 2021Pooled it
- Comparative Proteomics of Extracellular Vesicles of Two Species of Mucorales Reveals Species-Specific Cargo.Mycopathologia · 2026Article
- Transferrin Enhances Antifungal Therapy and Improves Survival in Experimental Mucormycosis.Journal of fungi (Basel, Switzerland) · 2026Article
- GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer (Review).International journal of molecular medicine · 2026Review
- Multimodal non-surgical management of isolated tracheobronchial mucormycosis: a case series of 8 patients.BMC infectious diseases · 2026Article
- Rhino-Orbital Mucormycosis Following COVID-19 Viral Vector Vaccination in an Immunocompetent Patient.Journal of fungi (Basel, Switzerland) · 2026Article
- Diabetes and Immunosuppression Drive Distinct Patterns ofbioRxiv : the preprint server for biology · 2026Article
- Molecular Mechanisms of Mucormycosis Pathogenesis: Host-Pathogen Interactions and Immune Evasion.Pathogens (Basel, Switzerland) · 2026Review
- How post-translational modifications in pathogenic fungi inform pathogenesis and immune responses.PLoS pathogens · 2026Article
- Light restores sporulation in Rhizopus microsporus cured of its endosymbionts, unveiling their role in fitness and virulence.The ISME journal · 2026Article
- Three hydrophobic surface binding a proteins link surface hydrophobicity to sporulation, biofilm formation, and host interaction inFrontiers in cellular and infection microbiology · 2026Article
- Secondary fungal infections in severe acute viral diseases: clinical features and underlying immune mechanisms.Frontiers in microbiology · 2026Review
- Article
- Blood protein thwarts deadly fungal disease.Nature · 2026Article
- A BRCT domain-containing protein induced in early phagocytosis plays a crucial role in the pathogenesis of the mucoralean Rhizopus microsporus.PLoS pathogens · 2026Article
- Chronic cutaneous and mucosal mucormycosis:Emerging microbes & infections · 2025Article
- The Unnoticed Threat: Clinical Characteristics, Risk Factors, and Outcome of Mucormycosis in Solid Organ Transplantation.Journal of fungi (Basel, Switzerland) · 2025Review
- The expression of fungal CotH, human glucose-regulated protein 78 (GRP78), and predicted miRNAs in macrophages and diabetic mice infected withMicrobiology spectrum · 2025Article
- A comprehensive in vitro and in silico assessment of eugenol glycoconjugates against azole and amphotericin B resistant Rhizopus spp.Molecular biology reports · 2025Article
102 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Angioinvasion is a hallmark of mucormycosis. Previously, we identified endothelial cell glucose-regulated protein 78 (GRP78) as a receptor for Mucorales that mediates host cell invasion. Here we determined that spore coat protein homologs (CotH) of Mucorales act as fungal ligands for GRP78. CotH proteins were widely present in Mucorales and absent from noninvasive pathogens. Heterologous expression of CotH3 and CotH2 in Saccharomyces cerevisiae conferred the ability to invade host cells via binding to GRP78. Homology modeling and computational docking studies indicated structurally compatible interactions between GRP78 and both CotH3 and CotH2. A mutant of Rhizopus oryzae, the most common cause of mucormycosis, with reduced CotH expression was impaired for invading and damaging endothelial cells and CHO cells overexpressing GRP78. This strain also exhibited reduced virulence in a diabetic ketoacidotic (DKA) mouse model of mucormycosis. Treatment with anti-CotH Abs abolished the ability of R. oryzae to invade host cells and protected DKA mice from mucormycosis. The presence of CotH in Mucorales explained the specific susceptibility of DKA patients, who have increased GRP78 levels, to mucormycosis. Together, these data indicate that CotH3 and CotH2 function as invasins that interact with host cell GRP78 to mediate pathogenic host-cell interactions and identify CotH as a promising therapeutic target for mucormycosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.