This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cummings, C. A. Articles by Miller, J. F. Search for Related Content PubMed PubMed Citation Articles by Cummings, C. A. Articles by Miller, J. F.

Species- and Strain-Specific Control of a Complex, Flexible Regulon by Bordetella BvgAS

C. A. Cummings,^1,2,* H. J. Bootsma,^3,, D. A. Relman,^1,2,4 and J. F. Miller^3,5

Departments of Microbiology and Immunology,¹ Medicine, Stanford University School of Medicine, Stanford, California 94305,⁴ VA Palo Alto Health Care System, Palo Alto, California, 94304,² Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, 90095,³ The Molecular Biology Institute, University of California, Los Angeles, California 90095⁵

Received 30 September 2005/ Accepted 12 December 2005

The Bordetella master virulence regulatory system, BvgAS, controls a spectrum of gene expression states, including the virulent Bvg⁺ phase, the avirulent Bvg^– phase, and at least one Bvg-intermediate (Bvgⁱ) phase. We set out to define the species- and strain-specific features of this regulon based on global gene expression profiling. Rather than functioning as a switch, Bvg controls a remarkable continuum of gene expression states, with hundreds of genes maximally expressed in intermediate phases between the Bvg⁺ and Bvg^– poles. Comparative analysis of Bvg regulation in B. pertussis and B. bronchiseptica revealed a relatively conserved Bvg⁺ phase transcriptional program and identified previously uncharacterized candidate virulence factors. In contrast, control of Bvg^–- and Bvgⁱ-phase genes diverged substantially between species; regulation of metabolic, transporter, and motility loci indicated an increased capacity in B. bronchiseptica, compared to B. pertussis, for ex vivo adaptation. Strain comparisons also demonstrated variation in gene expression patterns within species. Among the genes with the greatest variability in patterns of expression, predicted promoter sequences were nearly identical. Our data suggest that the complement of transcriptional regulators is largely responsible for transcriptional diversity. In support of this hypothesis, many putative transcriptional regulators that were Bvg regulated in B. bronchiseptica were deleted, inactivated, or unregulated by BvgAS in B. pertussis. We propose the concept of a "flexible regulon." This flexible regulon may prove to be important for pathogen evolution and the diversification of host range specificity.

Supplemental material for this article may be found at http://jb.asm.org/.

C.A.C. and H.J.B. contributed equally to this work.

Present address: Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.

This article has been cited by other articles:

• Marr, N., Tirsoaga, A., Blanot, D., Fernandez, R., Caroff, M. (2008). Glucosamine Found as a Substituent of Both Phosphate Groups in Bordetella Lipid A Backbones: Role of a BvgAS-Activated ArnT Ortholog. J. Bacteriol. 190: 4281-4290 [Abstract] [Full Text]  
• Brilli, M., Fani, R., Lio, P. (2008). Current trends in the bioinformatic sequence analysis of metabolic pathways in prokaryotes. Brief Bioinform 9: 34-45 [Abstract] [Full Text]  
• Williams, C. L., Cotter, P. A. (2007). Autoregulation Is Essential for Precise Temporal and Steady-State Regulation by the Bordetella BvgAS Phosphorelay. J. Bacteriol. 189: 1974-1982 [Abstract] [Full Text]  
• Diavatopoulos, D. A., Cummings, C. A., van der Heide, H. G. J., van Gent, M., Liew, S., Relman, D. A., Mooi, F. R. (2006). Characterization of a Highly Conserved Island in the Otherwise Divergent Bordetella holmesii and Bordetella pertussis Genomes. J. Bacteriol. 188: 8385-8394 [Abstract] [Full Text]  
• Nakamura, M. M., Liew, S.-Y., Cummings, C. A., Brinig, M. M., Dieterich, C., Relman, D. A. (2006). Growth Phase- and Nutrient Limitation-Associated Transcript Abundance Regulation in Bordetella pertussis.. Infect. Immun. 74: 5537-5548 [Abstract] [Full Text]  
• Irie, Y., Preston, A., Yuk, M. H. (2006). Expression of the Primary Carbohydrate Component of the Bordetella bronchiseptica Biofilm Matrix Is Dependent on Growth Phase but Independent of Bvg Regulation.. J. Bacteriol. 188: 6680-6687 [Abstract] [Full Text]  
• Brinig, M. M., Cummings, C. A., Sanden, G. N., Stefanelli, P., Lawrence, A., Relman, D. A. (2006). Significant Gene Order and Expression Differences in Bordetella pertussis Despite Limited Gene Content Variation.. J. Bacteriol. 188: 2375-2382 [Abstract] [Full Text]