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Infection and Immunity, June 2008, p. 2284-2295, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01540-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Analysis of the Actinobacillus pleuropneumoniae ArcA Regulon Identifies Fumarate Reductase as a Determinant of Virulence{triangledown} ,{dagger}

Falk F. R. Buettner,1 Ibrahim M. Bendallah,1 Janine T. Bosse,2 Karla Dreckmann,1 John H. E. Nash,3 Paul R. Langford,2 and Gerald-F. Gerlach1*

Department of Infectious Diseases, Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany,1 Department of Paediatrics, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom,2 Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada3

Received 21 November 2007/ Returned for modification 10 January 2008/ Accepted 23 March 2008

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.

* Corresponding author. Mailing address: Institut für Mikrobiologie, Zentrum für Infektionsmedizin, Stiftung Tierärztliche Hochschule Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany. Phone: 49 511 856 7598. Fax: 49 511 856 7697. E-mail: gfgerlach{at}gmx.de

{triangledown} Published ahead of print on 31 March 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. L. Flynn

Infection and Immunity, June 2008, p. 2284-2295, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01540-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bosse, J. T., Durham, A. L., Rycroft, A. N., Kroll, J. S., Langford, P. R. (2009). New Plasmid Tools for Genetic Analysis of Actinobacillus pleuropneumoniae and Other Pasteurellaceae. Appl. Environ. Microbiol. 75: 6124-6131 [Abstract] [Full Text]  


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