title: Host-iron assimilation: pathogenesis and novel therapies of mucormycosis.
abstract: Mucormycosis is a fungal infection caused by organisms belonging to the order Mucorales. Although considered uncommon, mucormycosis has been steadily increasing in incidents for the last two decades. Mortality of the disease is unacceptably high despite antifungal therapy and surgical interventions. The lack of understanding of the pathogenesis of the disease and the absence of rapid diagnostic assay contribute to the poor prognosis of mucormycosis. The hyper susceptibility of patients with elevated available serum iron points to the critical role of the ability of Mucorales to acquire host iron as a critical virulence factor. Specifically patients with deferoxamine-therapy, hyperglycaemic with or without ketoacidosis, or other forms of acidosis are uniquely predisposed to mucormycosis. In this review, we discuss the molecular mechanisms of infection in these patient categories in an attempt to identify novel therapies for a disease with poor prognosis. Emphasis on the effect of glucose and free iron on host-pathogen interactions are also covered.
authors.affiliation: The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center and the St. John's Cardiovascular Research Center, Torrance, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use; D000091342:Endoplasmic Reticulum Chaperone BiP; D054884:Host-Pathogen Interactions; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007501:Iron / Q000097:blood*; D007662:Ketosis / Q000150:complications; D009090:Mucorales; D009091:Mucormycosis / Q000188:drug therapy* / Q000473:pathology*; D012307:Risk Factors; D037521:Virulence Factors
chemical_list: D000935:Antifungal Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D037521:Virulence Factors; D007501:Iron
keywords: CotH; DKA; GRP78; deferoxamine; iron uptake; mucormycosis