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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yang, Menghua Selamoglu, Nur Kan, Biao Liu, Zhi Zhu, Jun Peterfreund, Gregory L. Zhong, Zengtao Tsou, Amy M. Daldal, Fevzi |
| Description | Author Affiliation: Liu Z ( Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.); |
| Abstract | Bacterial pathogens have evolved sophisticated signal transduction systems to coordinately control the expression of virulence determinants. For example, the human pathogen Vibrio cholerae is able to respond to host environmental signals by activating transcriptional regulatory cascades. The host signals that stimulate V. cholerae virulence gene expression, however, are still poorly understood. Previous proteomic studies indicated that the ambient oxygen concentration plays a role in V. cholerae virulence gene expression. In this study, we found that under oxygen-limiting conditions, an environment similar to the intestines, V. cholerae virulence genes are highly expressed. We show that anaerobiosis enhances dimerization and activity of AphB, a transcriptional activator that is required for the expression of the key virulence regulator TcpP, which leads to the activation of virulence factor production. We further show that one of the three cysteine residues in AphB, C(235), is critical for oxygen responsiveness, as the AphB(C235S) mutant can activate virulence genes under aerobic conditions in vivo and can bind to tcpP promoters in the absence of reducing agents in vitro. Mass spectrometry analysis suggests that under aerobic conditions, AphB is modified at the C(235) residue. This modification is reversible between oxygen-rich aquatic environments and oxygen-limited human hosts, suggesting that V. cholerae may use a thiol-based switch mechanism to sense intestinal signals and activate virulence. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Bacterial Proteins Metabolism Gene Expression Regulation, Bacterial Sulfhydryl Compounds Chemistry Trans-Activators Vibrio Cholerae Genetics Anaerobiosis Cysteine Gene Expression Profiling Mutation Oxygen Promoter Regions, Genetic Proteomics Transcription, Genetic Transcriptional Activation Pathogenicity Virulence Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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