Hfq, a Novel Pleiotropic Regulator of Virulence-Associated Genes in Francisella tularensis▿
| Autor: | Khaled Alkhuder, Anna-Lena Forslund, Åke Forsberg, Karin L. Meibom, Kerstin Kuoppa, Alain Charbit, Iharilalao Dubail, Marion Dupuis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Genomic Islands
Operon Virulence Factors Immunology Molecular Sequence Data Virulence Down-Regulation Host Factor 1 Protein Microbiology Tularemia Mice Bacterial Proteins Stress Physiological Gene Order medicine Animals Humans Amino Acid Sequence Francisella tularensis Gene Regulator gene Oligonucleotide Array Sequence Analysis Genetics Mice Inbred BALB C biology Gene Expression Profiling Bacterial Infections Gene Expression Regulation Bacterial biology.organism_classification medicine.disease Pathogenicity island Survival Analysis Infectious Diseases Francisella Parasitology Female Sequence Alignment |
| Popis: | Francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the Francisella pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in F. tularensis involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in F. tularensis and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the F. tularensis vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of F. tularensis , FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in F. tularensis , acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|