Petrikkos G, Tsioutis C, et al.
Clinical therapeutics. Date of publication 2018 Jun 1;volume 40(6):894-902.
1. Clin Ther. 2018 Jun;40(6):894-902. doi: 10.1016/j.clinthera.2018.03.009. Epub
2018 Apr 6.
Recent Advances in the Pathogenesis of Mucormycoses.
Petrikkos G(1), Tsioutis C(2).
Author information:
(1)School of Medicine, European University Cyprus, Nicosia, Cyprus; Infectious
Diseases Research Laboratory, Fourth Dept of Internal Medicine, University
General Hospital Attikon, Medical School, National and Kapodistrian University of
Athens, Athens, Greece. Electronic address: g.petrikkos@euc.ac.cy.
(2)School of Medicine, European University Cyprus, Nicosia, Cyprus.
PURPOSE: The purposes of this review are to describe the pathogenesis of
mucormycosis and to address recent research advances in understanding the
mechanisms of fungal invasion and dissemination.
METHODS: Studies and reviews published in the PubMed and ClinicalTrials.gov
databases until December 2017 that explored or reported recent advances in the
understanding of the pathogenesis of mucormycosis were reviewed.
FINDINGS: To cause disease, fungal spores need to evade the innate immune system
and germinate, leading to angioinvasion and tissue destruction. Recent studies
have found that Mucorales are able to downregulate several host defense
mechanisms and have identified the specific receptors through which Mucorales
attach to the endothelium, facilitating their endocytosis and subsequent
angioinvasion. In addition, certain conditions found to act through various
mechanisms and pathways in experimental and animal studies, such as
hyperglycemia, elevated iron concentrations, and acidosis (particularly diabetic
ketoacidosis), increase the virulence of the fungi and enhance their attachment
to the endothelium, rendering patients with uncontrolled diabetes and patients
with iron overload susceptible to mucormycosis. The role and various antifungal
functions of platelets and natural killer cells are highlighted, and the
potential contribution of alternative therapies, such as manipulating the innate
immune host defenses with granulocyte transfusions or administration of growth
factors and using the antifungal effects of calcineurin inhibitors, are
presented. Finally, directions and possible implications for future research are
provided.
IMPLICATIONS: This article provides a comprehensive overview of research advances
in the pathogenesis of infections caused by Mucorales and helps future studies
develop effective treatment strategies and improve patient outcomes.
Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.
DOI: 10.1016/j.clinthera.2018.03.009
PMID: 29631910
