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Infection and Immunity, October 2006, p. 5537-5548, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00781-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Growth Phase- and Nutrient Limitation-Associated Transcript Abundance Regulation in Bordetella pertussis

Mari M. Nakamura,^1, Sin-Yee Liew,^2,3 Craig A. Cummings,^2,3,4 Mary M. Brinig,^2,3 Christine Dieterich ,^2, and David A. Relman^2,3,4*

Departments of Pediatrics/Infectious Diseases,¹ Microbiology and Immunology,² Medicine, Stanford University, Stanford, California,³ Veteran Affairs Palo Alto Health Care System, Palo Alto, California⁴

Received 15 May 2006/ Returned for modification 16 June 2006/ Accepted 6 July 2006

To survive in a host environment, microbial pathogens must sense local conditions, including nutrient availability, and adjust their growth state and virulence functions accordingly. No comprehensive investigation of growth phase-related gene regulation in Bordetella pertussis has been reported previously. We characterized changes in genome-wide transcript abundance of B. pertussis as a function of growth phase and availability of glutamate, a key nutrient for this organism. Using a Bordetella DNA microarray, we discovered significant changes in transcript abundance for 861 array elements during the transition from log phase to stationary phase, including declining transcript levels of many virulence factor genes. The responses to glutamate depletion exhibited similarities to the responses induced by exit from log phase, including decreased virulence factor transcript levels. However, only 23% of array elements that showed at least a fourfold growth phase-associated difference in transcript abundance also exhibited glutamate depletion-associated changes, suggesting that nutrient limitation may be one of several interacting factors affecting gene regulation during stationary phase. Transcript abundance patterns of a Bvg⁺ phase-locked mutant revealed that the BvgAS two-component regulatory system is a key determinant of growth phase- and nutrient limitation-related transcriptional control. Several adhesin genes exhibited lower transcript abundance during stationary phase and under glutamate restriction conditions. The predicted bacterial phenotype was confirmed: adherence to bronchoepithelial cells decreased 3.3- and 4.4-fold at stationary phase and with glutamate deprivation, respectively. Growth phase and nutrient availability may serve as cues by which B. pertussis regulates virulence according to the stage of infection or the location within the human airway.

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

Editor: D. L. Burns

Present address: Children’s Hospital Boston, Boston, MA 02115.