Influence of hypoxia on antifungal susceptibility , sterol pattern and biomarker release of Aspergillus spp.

Ref ID: 19491

Author:

U Binder1*, E Maurer1, C Müller2, F Bracher2, C Lass-Flörl1

Author address:

1Division of Hygiene and Medical Microbiology, Medical University Innsbruck, Innsbruck, Austria
2Department of Pharmacy, Ludwig Maximilians University Munich, Munich, Germany

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Objectives:
Invasive aspergillosis (IA) is a major life-threatening disease in immunocompromised patients,
with mortality rates from 40% up to 90% in high-risk populations. The most common species
causing aspergillosis is Aspergillus (A.) fumigatus, accounting for approximately 90% of infections.
Depending on regional distinctions, A. flavus and A. terreus are frequently reported. During infection,
fungal pathogens must adapt to microenvironmental stresses, including hypoxia as well as high CO2
levels. Such oxystress conditions are usually not taken into account in current in vitro models of
infection, the assessment of antifungal sensitivities or the release of biomarkers used for diagnosis.
Methods:
Using Etest strips, the in vitro activity of amphotericin B (amB), different azoles and echinocandins
in hypoxic conditions (1% O2, 5% CO2) to their activity in normoxic conditions against aspergilli.
For evaluation of biomarker release, the amount of β -1,3 glucan (BG) and galactomannan (GM)
in Aspergillus supernatants was determined by commercially available detection kits (Platelia/
Fungitell).
Changes in the sterol pattern or the amount of ergosterol was evaluated by GC-MS.
Results:
On surface cultures, we found a reduction of the minimal inhibitory concentration (MIC) for amB
for all aspergilli in hypoxic conditions. Similarly, a significant reduction in the MIC for all tested
azoles was demonstrated for A. terreus isolates, while for A. fumigatus isolates differences were less
pronounced. For echinocandins, little or no change in the MEC (minimal effective concentration)
was detected between hypoxic and normoxic conditions for all aspergilli. Most interestingly, A.
terreus strains, that are resistant to amB in normoxia, exhibited sensitivity to amB in hypoxic
conditions, defining a breakpoint of > 2 μg/ml. Notably, for none of the strains tested, MIC/MEC
values increased in hypoxia. Our results so far indicate, that there is no significant difference in the
amount of ergosterol whether mycelia is grown in hypoxia or normoxia.
The detection of circulating fungal antigens in serumfor Aspergillus galactomannanor β -D-glucan
has become an accepted diagnostic strategy. However, sensitivity and specificity vary extremely and
the reasons are only partially clear; therefore, we are currently checking whether hypoxia influences
the physiological kinetics of GM and íŸ-glucan release.
Conclusion:
ECOFFs in hypoxia differ from those in normoxia for antifungal drugs targeting ergosterol or its
biosynthesis. Supplementation of test media with blood or ergosterol abrogated the reduction of the
MIC, but there is no direct link between ergosterol content and increased susceptibility to amB and
azoles, but further analysis of sterol intermediates needs to be done in more detail.

Abstract Number: 19

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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