Susceptibility of Pneumocystis to Echinocandins in Suspension and Biofilm Cultures

Abstract

ABSTRACTThe targeted inhibition of cyst but not trophic development by anidulafungin, caspofungin, and micafungin onPneumocystis murinaandPneumocystis cariniiin rodent models ofPneumocystis cariniipneumonia (PCP) was recently reported by us (M. T. Cushion et al., PLoS One 5:e8524, 2010). To better understand the effects of echinocandins onP. 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 ofPneumocystisin 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-Pneumocystisactivities of the echinocandins in bothin vitrosystems.