critical role of bcr1-dependent adhesins in c. albicans biofilm formation in vitro and in vivo关键作用的bcr1-dependent丰富的白念珠菌生物膜形成体外和体内.pdf

Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation In Vitro and In Vivo 1,2 3 3 1 4 4 Clarissa J. Nobile , David R. Andes , Jeniel E. Nett , Frank J. Smith, Jr. , Fu Yue , Quynh-Trang Phan , John E. Edwards, Jr.4,5, Scott G. Filler4,5, Aaron P. Mitchell1* 1 Department of Microbiology, Columbia University, New York, New York, United States of America, 2 Biological Sciences Program, Department of Biological Sciences, Columbia University, New York, New York, United States of America, 3 Department of Medicine, Section of Infectious Diseases, University of Wisconsin, Madison, Wisconsin, United States of America, 4 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America, 5 The David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America The fungal pathogen Candida albicans is frequently associated with catheter-based infections because of its ability to form resilient biofilms. Prior studies have shown that the transcription factor Bcr1 governs biofilm formation in an in vitro catheter model. However, the mechanistic role of the Bcr1 pathway and its relationship to biofilm formation in vivo are unknown. Our studies of biofilm formation in vitro indicate that the surface protein Als3, a known adhesin, is a key target under Bcr1 control. We show that an als3/als3 mutant is biofilm-defective in vitro, and that ALS3 overexpression rescues the biofilm defect of the bcr1/bcr1 mutant. We extend these findings with an in vivo venous catheter model. The bcr1/bcr1 mutant is unable to populate the catheter surface, though its virulence suggests that it has no growth defect in vivo. ALS3 overexpression rescues the bcr1/bcr1 biof