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Invasive Mold Infections: Virulence and Pathogenesis of Mucorales

DOI: 10.1155/2012/349278

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Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses. 1. Introduction The Mucorales, which is the core group of the traditional Zygomycota [1–3], have been recently reclassified into the subphylum Mucoromycotina of the Glomeromycota phylum of the kingdom Fungi [4]. This new classification does not include Zygomycota, because the authors consider the phylum polyphyletic, indeed the name zygomycosis, which encompassed infections caused by members of Mucorales and Entomophthorales, has become obsolete [4]. The Mucorales are characterized by aseptate (coenocytic) hyaline hyphae, sexual reproduction with the formation of zygospores, and asexual reproduction with nonmotile sporangiospores. They are ubiquitous in nature, being found in food, vegetation, and soil [1–3]. The majority of the invasive diseases are caused by genera of the Mucoraceae family, and the resulted disease is called mucormycosis [1–3, 5–7]. Transmission occurs by inhalation of aerosolized spores, ingestion of contaminated foodstuffs, or through cutaneous exposure, the latter being the most important mode of acquisition of mucormycosis in immunocompetent hosts [6, 8]. Risk factors for invasive diseases include uncontrolled diabetes mellitus, haematological malignancies, bone marrow and solid organ transplantation, deferoxamine therapy, corticosteroid therapy, or other underlying conditions impairing the immune system [9]. Limited activity of some principal classes of antifungal drugs (i.e., echinocandins and azole derivatives) as well as vascular invasion and neurotropic activity could explain the high mortality seen in

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