title: Susceptibility of Pneumocystis to echinocandins in suspension and biofilm cultures.
abstract: The targeted inhibition of cyst but not trophic development by anidulafungin, caspofungin, and micafungin on Pneumocystis murina and Pneumocystis carinii in rodent models of Pneumocystis carinii pneumonia (PCP) was recently reported by us (M. T. Cushion et al., PLoS One 5:e8524, 2010). To better understand the effects of echinocandins on P. carinii, the same three compounds were evaluated in standard suspension and biofilm cultures supplemented with various concentrations of sera using the measurement of ATP as the indicator. In suspension cultures with 1 and 5% serum, anidulafungin was the most active compound but 10 and 20% serum abrogated the efficacy of all three echinocandins. Established biofilm cultures that included both the nonadherent and adherent phases were more resistant to micafungin than caspofungin regardless of serum concentration, while anidulafungin had significant activity at 1 and 5% serum concentrations. Nascent biofilms were mostly affected by anidulafungin in 1 and 5% serum, but none of the compounds showed significant activity in 20% serum. We show for the first time that (i) echinocandins differ in their abilities to deplete the ATP of Pneumocystis in biofilms and in suspension cultures, (ii) this variability mostly reflected the reported efficacies in animal models of infection, and (iii) high serum levels decreased the anti-Pneumocystis activities of the echinocandins in both in vitro systems.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Melanie.cushion@va.gov
authors.forename: Melanie T
authors.initials: MT
authors.lastname: Cushion
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Collins
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D055666:Lipopeptides / Q000494:pharmacology; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D016720:Pneumocystis Infections / Q000188:drug therapy; D045363:Pneumocystis carinii / Q000187:drug effects*; D051381:Rats
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000255:Adenosine Triphosphate; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin