Pathogenesis of Mucormycosis

Abstract

Mucormycosis is a life-threatening infection that occurs in patients who are immunocompromised because of diabetic ketoacidosis, neutropenia, organ transplantation, and/or increased serum levels of available iron. Because of the increasing prevalence of diabetes mellitus, cancer, and organ transplantation, the number of patients at risk for this deadly infection is increasing. Despite aggressive therapy, which includes disfiguring surgical debridement and frequently adjunctive toxic antifungal therapy, the overall mortality rate is high. New strategies to prevent and treat mucormycosis are urgently needed. Understanding the pathogenesis of mucormycosis and the host response to invading hyphae ultimately will provide targets for novel therapeutic interventions. In this supplement, we review the current knowledge about the virulence traits used by the most common etiologic agent of mucormycosis, Rhizopus oryzae. Because patients with elevated serum levels of available iron are uniquely susceptible to mucormycosis and these infections are highly angioinvasive, emphasis is placed on the ability of the organism to acquire iron from the host and on its interactions with endothelial cells lining blood vessels. Several promising therapeutic strategies in preclinical stages are identified.

Primary Gangrenous Cutaneous Mold Infections in a Patient with Cancer and Neutropenia

“…27 Severe neutropenia with an ANC of less than 500 cells/mm 3 increases susceptibility to bacterial or fungal infections. 28 29 By contrast, patients with HIV/AIDS do not appear to be at increased risk for developing mucormycosis. 29 Therefore, neutrophils -but not necessarily T-cell lymphocytes -are critical for inhibiting fungal-spore proliferation.…”

“…28 29 By contrast, patients with HIV/AIDS do not appear to be at increased risk for developing mucormycosis. 29 Therefore, neutrophils -but not necessarily T-cell lymphocytes -are critical for inhibiting fungal-spore proliferation. 29 Cutaneous mucormycosis is an increasingly prevalent form of mucormycosis that has been predominantly described in immunocompromised patients who are recipients of transplants, including both hematopoietic stem cell and solid organ transplants after minor trauma.…”

“…29 Therefore, neutrophils -but not necessarily T-cell lymphocytes -are critical for inhibiting fungal-spore proliferation. 29 Cutaneous mucormycosis is an increasingly prevalent form of mucormycosis that has been predominantly described in immunocompromised patients who are recipients of transplants, including both hematopoietic stem cell and solid organ transplants after minor trauma. 30,31 Some studies suggest that the incidence of zygomycosis appears to be increasing in oncology centers and specifically in patient populations receiving hematopoietic stem cell transplants, possibly related to the use of voriconazole prophylaxis.…”

Differentiation of clinically relevant Mucorales Rhizopus microsporus and R. arrhizus by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)

“…The disease is angioinvasive, leading to thrombosis and extended necrosis, and is rapidly progressive with high rates of mortality (w50%), that approach 100% among patients with disseminated disease or those with persistent neutropenia. Clinical manifestation of the disease occurs as rhinocerebral, pulmonary, gastrointestinal, renal or disseminated infection (Ibrahim et al, 2012). The number of cases is increasing, especially in patients with impaired immunity due to e.g.…”

Mucormycoses

“…L'élévation de la glycémie ou du taux sanguin en fer favoriserait l'expression de la GRP78. Cela pourrait expliquer en partie la susceptibilité de la population des diabétiques aux mucormycoses [5]. L'approche thérapeutique des mucormycoses est pluridisciplinaire et repose sur un tryptique : correction des facteurs favorisants, prise en charge chirurgicale majeure et rapide et traitement antifongique.…”