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Infection and Immunity, May 2009, p. 2113-2124, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01205-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Listeria monocytogenes {sigma}B Modulates PrfA-Mediated Virulence Factor Expression{triangledown} ,{dagger}

Juliane Ollinger, Barbara Bowen, Martin Wiedmann, Kathryn J. Boor, and Teresa M. Bergholz*

Department of Food Science, Cornell University, Ithaca, New York 14853

Received 29 September 2008/ Returned for modification 2 November 2008/ Accepted 19 February 2009

Listeria monocytogenes {sigma}B and positive regulatory factor A (PrfA) are pleiotropic transcriptional regulators that coregulate a subset of virulence genes. A positive regulatory role for {sigma}B in prfA transcription has been well established; therefore, observations of increased virulence gene expression and hemolytic activity in a {Delta}sigB strain initially appeared paradoxical. To test the hypothesis that L. monocytogenes {sigma}B contributes to a regulatory network critical for appropriate repression as well as induction of virulence gene expression, genome-wide transcript profiling and follow-up quantitative reverse transcriptase PCR (qRT-PCR), reporter fusion, and phenotypic experiments were conducted using L. monocytogenes prfA*, prfA* {Delta}sigB, {Delta}prfA, and {Delta}prfA {Delta}sigB strains. Genome-wide transcript profiling and qRT-PCR showed that in the presence of active PrfA (PrfA*), {sigma}B is responsible for reduced expression of the PrfA regulon. {sigma}B-dependent modulation of PrfA regulon expression reduced the cytotoxic effects of a PrfA* strain in HepG2 cells, highlighting the functional importance of regulatory interactions between PrfA and {sigma}B. The emerging model of the role of {sigma}B in regulating overall PrfA activity includes a switch from transcriptional activation at the P2prfA promoter (e.g., in extracellular bacteria when PrfA activity is low) to posttranscriptional downregulation of PrfA regulon expression (e.g., in intracellular bacteria when PrfA activity is high).


* Corresponding author. Mailing address: Department of Food Science, Cornell University, 405 Stocking Hall, Ithaca, NY 14853. Phone: (607) 255-1266. Fax: (607) 254-4868. E-mail: tmb224{at}cornell.edu

{triangledown} Published ahead of print on 2 March 2009.

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

Editor: A. Camilli


Infection and Immunity, May 2009, p. 2113-2124, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01205-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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