role of bcr1-activated genes hwp1 and hyr1 in candida albicans oral mucosal biofilms and neutrophil evasionhwp1 bcr1-activated基因的作用和hyr1白色念珠菌口腔黏膜生物膜和中性粒细胞逃税.pdfVIP

Role of Bcr1-Activated Genes Hwp1 and Hyr1 in Candida Albicans Oral Mucosal Biofilms and Neutrophil Evasion 2 1 1 1 3 Prabhat Dwivedi , Angela Thompson , Zhihong Xie , Helena Kashleva , Shantanu Ganguly , Aaron P. 3 1 Mitchell , Anna Dongari-Bagtzoglou * 1 Division of Periodontology, School of Dental Medicine, University of Connecticut, Farmington, Connecticut, United States of America, 2 Department of Microbiology, University of Texas, Houston, Texas, United States of America, 3 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America Abstract Candida albicans triggers recurrent infections of the oropharyngeal mucosa that result from biofilm growth. Prior studies have indicated that the transcription factor Bcr1 regulates biofilm formation in a catheter model, both in vitro and in vivo. We thus hypothesized that Bcr1 plays similar roles in the formation of oral mucosal biofilms and tested this hypothesis in a mouse model of oral infection. We found that a bcr1/bcr1 mutant did not form significant biofilm on the tongues of immunocompromised mice, in contrast to reference and reconstituted strains that formed pseudomembranes covering most of the tongue dorsal surface. Overexpression of HWP1, which specifies an epithelial adhesin that is under the transcriptional control of Bcr1, partly but significantly rescued the bcr1/bcr1 biofilm phenotype in vivo. Since HWP1 overexpression only partly reversed the biofilm phenotype, we investigated whether additional mechanisms, besides adhesin down-regulation, were responsible for the reduced virulence of this