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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wei, Zhengyu Zenewicz, Lauren A. Goldfine, Howard |
| Description | Author Affiliation: Wei Z ( Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.); |
| Abstract | Listeria monocytogenes phosphatidylinositol-specific phospholipase C (PI-PLC) plays a critical role in escape of this human pathogen from host cell vacuoles. Unlike classical bacterial PI-PLCs, the L. monocytogenes enzyme has very weak activity on glycosylphosphatidylinositol (GPI)-anchored proteins. Previous crystal structure analysis has revealed that a small beta-strand (Vb) is present in Bacillus cereus PI-PLC and is absent in the enzyme from L. monocytogenes. This Vb beta-strand in B. cereus PI-PLC forms contacts with the glycan linker of GPI anchors, which presumably increases its activity on GPI-anchored proteins. In this study, we show that, of all known bacterial PI-PLCs, those from listeriae are the only ones that lack the beta-strand. Expression by L. monocytogenes of B. cereus PI-PLC, which has strong activity on GPI-anchored proteins, inhibited bacterial escape from a vacuole and cell-to-cell spread, resulting in greatly reduced virulence in mice. Deletion of the Vb beta-strand from B. cereus PI-PLC abolished its ability to cleave GPI-anchored proteins, decreased its inhibitory effects, and increased its virulence in mice. These results strongly suggest that L. monocytogenes PI-PLC has evolved as an important determinant of L. monocytogenes pathogenesis by absence of the Vb beta-strand, thus leading to greatly reduced activity on GPI-anchored proteins. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 36 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glycosylphosphatidylinositols Metabolism Listeria Monocytogenes Enzymology Pathogenicity Phosphatidylinositol Diacylglycerol-Lyase Amino Acid Sequence Animals Cell Line Cell Proliferation Gene Deletion Gene Expression Regulation, Bacterial Gene Expression Regulation, Enzymologic Cytology Genetics Mice Molecular Sequence Data Chemistry Phosphoinositide Phospholipase C Protein Structure, Secondary Sequence Alignment Virulence Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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