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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Neely, Alice N. Brencic, Anja Liberati, Nicole Miyata, Sachiko Hyodo, Mamoru Lee, Vincent Urbach, Jonathan Hayakawa, Yoshihiro Lory, Stephen Ausubel, Frederick M. Kulasakara, Hemantha Lee, Daniel G. |
| Description | Author Affiliation: Kulasakara H ( Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.); |
| Abstract | The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Bacterial Proteins Metabolism Cyclic GMP Analogs & Derivatives Phosphoric Diester Hydrolases Phosphorus-Oxygen Lyases Pseudomonas Aeruginosa Enzymology Pathogenicity Genetics Biofilms Growth & Development Physiology Escherichia Coli Proteins Genes, Bacterial Genome, Bacterial Genomics Mutation Phenotype Chemistry Protein Structure, Tertiary Pseudomonas Infections Microbiology 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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