• Medientyp: E-Artikel
  • Titel: Mutations in hmg1 , Challenging the Paradigm of Clinical Triazole Resistance in Aspergillus fumigatus
  • Beteiligte: Rybak, Jeffrey M.; Ge, Wenbo; Wiederhold, Nathan P.; Parker, Josie E.; Kelly, Steven L.; Rogers, P. David; Fortwendel, Jarrod R.
  • Erschienen: American Society for Microbiology, 2019
  • Erschienen in: mBio
  • Sprache: Englisch
  • DOI: 10.1128/mbio.00437-19
  • ISSN: 2161-2129; 2150-7511
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> <jats:named-content content-type="genus-species">Aspergillus fumigatus</jats:named-content> is the predominant pathogen of invasive aspergillosis, a disease state credited with over 200,000 life-threatening infections annually. The triazole class of antifungals are clinically essential to the treatment of invasive aspergillosis. Unfortunately, resistance to the triazoles among <jats:named-content content-type="genus-species">A. fumigatus</jats:named-content> isolates is now increasingly reported worldwide. In this work, we challenge the current paradigm of clinical triazole resistance in <jats:named-content content-type="genus-species">A. fumigatus</jats:named-content> , by first demonstrating that previously characterized mechanisms of resistance have nominal impact on triazole susceptibility and subsequently identifying a novel mechanism of resistance with a profound impact on clinical triazole susceptibility. We demonstrate that mutations in the HMG-CoA reductase gene, <jats:italic>hmg1</jats:italic> , are common among resistant clinical isolates and that <jats:italic>hmg1</jats:italic> mutations confer resistance to all clinically available triazole antifungals. </jats:p>
  • Zugangsstatus: Freier Zugang