Erschienen:
American Society for Microbiology, 2015
Erschienen in:Antimicrobial Agents and Chemotherapy
Sprache:
Englisch
DOI:
10.1128/aac.00957-15
ISSN:
0066-4804;
1098-6596
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>ABSTRACT</jats:title>
<jats:p>
<jats:italic>N</jats:italic>
-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Scedosporium</jats:named-content>
and
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Lomentospora</jats:named-content>
, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Scedosporium apiospermum</jats:named-content>
,
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Scedosporium boydii</jats:named-content>
, and
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Lomentospora prolificans</jats:named-content>
(formerly
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Scedosporium prolificans</jats:named-content>
) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log
<jats:sub>10</jats:sub>
reduction in CFU after 4 h and a 4- to >6-log
<jats:sub>10</jats:sub>
reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Galleria mellonella</jats:named-content>
infected with 1.0 × 10
<jats:sup>7</jats:sup>
conidia of
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. apiospermum</jats:named-content>
and
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. boydii</jats:named-content>
died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Scedosporium</jats:named-content>
and
<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Lomentospora</jats:named-content>
species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.
</jats:p>