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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>