echinocandin treatment of pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infectionechinocandin治疗肺孢子菌肺炎在动物模型中耗尽囊肿离开营养不能传播感染的负担.pdfVIP

Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection 1,2 2 1,2 1,2 1,2 Melanie T. Cushion *, Michael J. Linke , Alan Ashbaugh , Tom Sesterhenn , Margaret S. Collins , 1,2 3 1,2 Keeley Lynch , Ronald Brubaker , Peter D. Walzer 1 College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America, 2 Veterans Administration Medical Center, Cincinnati, Ohio, United States of America, 3 Department of Pathology, The Christ Hospital, Cincinnati, Ohio, United States of America Abstract Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co- morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express b -1,3-D-glucan synthetase and contain abundant b -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of b -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin tre