Growth phase- and nutrient limitation-associated transcript abundance regulation in Bordetella pertussis.
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.
Nakamura
Mari M
MM
Department of Pediatrics/Infectious Diseases, Stanford University, Stanford, California, USA.
Liew
Sin-Yee
SY
Cummings
Craig A
CA
Brinig
Mary M
MM
Dieterich
Christine
C
Relman
David A
DA
D001426:Bacterial Proteins / Q000235:genetics; D001886:Bordetella pertussis / Q000235:genetics* / Q000254:growth & development*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D018698:Glutamic Acid / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D018698:Glutamic Acid