title: How does antifungal pharmacology differ for mucormycosis versus aspergillosis?
abstract: Over the last decade, advances in diagnostic systems and the introduction of new antifungal agents have significantly improved outcomes in immunocompromised patients who develop invasive aspergillosis. However, mortality rates remain relatively unchanged for less common, but highly aggressive, mold infections such as mucormycosis. Recent genome sequencing of Rhizopus oryzae revealed evidence of a whole-genome duplication event during the evolution of this pathogen. Consequently, R. oryzae has a 2- to 10-fold enrichment in gene families associated with ergosterol and cell wall biosynthesis, cell growth, iron uptake, and known fungal virulence factors compared with sequenced Aspergillus fumigatus strains. This genetic plasticity may explain the remarkable capability of this pathogen for rapid growth in hostile environments, such as the inflammatory milieu, as well as its relative resistance to multiple antifungal classes. Herein, we examine how pharmacological aspects of treating mucormycosis may differ from those of the more commonly encountered invasive aspergillosis.
authors.affiliation: Department of College of Pharmacy, The University of Houston, TX 77030, USA. rlewis@uh.edu
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000235:genetics / Q000472:pathogenicity; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D026141:Drug Resistance, Multiple, Fungal; D004875:Ergosterol / Q000096:biosynthesis / Q000235:genetics; D020440:Gene Duplication; D016681:Genome, Fungal; D042822:Genomic Instability; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009091:Mucormycosis / Q000188:drug therapy* / Q000382:microbiology; D011743:Pyrimidines / Q000494:pharmacology; D012233:Rhizopus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D013045:Species Specificity; D014230:Triazoles / Q000494:pharmacology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D037521:Virulence Factors; D017964:Itraconazole; D000666:Amphotericin B; D065819:Voriconazole; D004875:Ergosterol