| Analysis of the Actinobacillus pleuropneumoniae ArcA regulon identifies fumarate reductase as a determinant of virulence. | |
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MedLine Citation:
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PMID: 18378638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ability of the bacterial pathogen Actinobacillus pleuropneumoniae to grow anaerobically allows the bacterium to persist in the lung. The ArcAB two-component system is crucial for metabolic adaptation in response to anaerobic conditions, and we recently showed that an A. pleuropneumoniae arcA mutant had reduced virulence compared to the wild type (F. F. Buettner, A. Maas, and G.-F. Gerlach, Vet. Microbiol. 127:106-115, 2008). In order to understand the attenuated phenotype, we investigated the ArcA regulon of A. pleuropneumoniae by using a combination of transcriptome (microarray) and proteome (two-dimensional difference gel electrophoresis and subsequent mass spectrometry) analyses. We show that ArcA negatively regulates the expression of many genes, including those encoding enzymes which consume intermediates during fumarate synthesis. Simultaneously, the expression of glycerol-3-phosphate dehydrogenase, a component of the respiratory chain serving as a direct reduction equivalent for fumarate reductase, was upregulated. This result, together with the in silico analysis finding that A. pleuropneumoniae has no oxidative branch of the citric acid cycle, led to the hypothesis that fumarate reductase might be crucial for virulence by providing (i) energy via fumarate respiration and (ii) succinate and other essential metabolic intermediates via the reductive branch of the citric acid cycle. To test this hypothesis, an isogenic A. pleuropneumoniae fumarate reductase deletion mutant was constructed and studied by using a pig aerosol infection model. The mutant was shown to be significantly attenuated, thereby strongly supporting a crucial role for fumarate reductase in the pathogenesis of A. pleuropneumoniae infection. |
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Authors:
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Falk F R Buettner; Ibrahim M Bendallah; Janine T Bosse; Karla Dreckmann; John H E Nash; Paul R Langford; Gerald-F Gerlach |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-03-31 |
Journal Detail:
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Title: Infection and immunity Volume: 76 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-05-20 Completed Date: 2008-07-03 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 2284-95 Citation Subset: IM |
Affiliation:
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Department of Infectious Diseases, Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actinobacillus Infections
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immunology,
microbiology Actinobacillus pleuropneumoniae / enzymology*, genetics, immunology, pathogenicity* Animals Bacterial Proteins / genetics, metabolism Gene Expression Profiling Gene Expression Regulation, Bacterial / physiology Male Random Allocation Regulon / genetics, physiology* Specific Pathogen-Free Organisms Succinate Dehydrogenase / genetics, metabolism* Swine Virulence |
| Grant Support | |
ID/Acronym/Agency:
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BBS/B/08132//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; EC 1.3.99.1/Succinate Dehydrogenase |
| Comments/Corrections | |
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