Signature Motifs Identify an Acinetobacter Cif Virulence Factor with Epoxide Hydrolase Activity
| Autor: | Kelli L. Hvorecny, Kyle C. Cady, Jennifer M. Bomberger, Alicia E. Ballok, Andrew A. Bridges, Christopher D. Bahl, George A. O'Toole, Dean R. Madden |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Acinetobacter baumannii
Models Molecular Transcription Genetic Virulence Factors Amino Acid Motifs Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator Endocytic recycling Biology Crystallography X-Ray medicine.disease_cause Microbiology Biochemistry Substrate Specificity Bacterial Proteins Hydrolase medicine Amino Acid Sequence Epoxide hydrolase Molecular Biology Epoxide Hydrolases Acinetobacter Sequence Homology Amino Acid Pseudomonas aeruginosa Cell Biology respiratory system Apical membrane biology.organism_classification Molecular biology Endocytosis respiratory tract diseases Protein Structure Tertiary Epoxide hydrolase activity Mutagenesis Site-Directed Gene Deletion Plasmids Acinetobacter nosocomialis |
| Zdroj: | Journal of Biological Chemistry. 289:7460-7469 |
| ISSN: | 0021-9258 |
| Popis: | Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii ("aCif"). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog ("aCifR") and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|