Host-iron assimilation: pathogenesis and novel therapies of mucormycosis

Mycoses. 2014 Dec;57 Suppl 3(0 3):13-7. doi: 10.1111/myc.12232. Epub 2014 Sep 1.

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.

Keywords: CotH; DKA; GRP78; deferoxamine; iron uptake; mucormycosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antifungal Agents / therapeutic use
  • Endoplasmic Reticulum Chaperone BiP
  • Host-Pathogen Interactions*
  • Humans
  • Hyperglycemia / complications
  • Iron / blood*
  • Ketosis / complications
  • Mucorales
  • Mucormycosis / drug therapy*
  • Mucormycosis / pathology*
  • Risk Factors
  • Virulence Factors

Substances

  • Antifungal Agents
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Virulence Factors
  • Iron