Role of feedback and network architecture in controlling virulence gene expression in Bordetella.
Bordetella is a Gram-negative bacterium responsible for causing whooping cough in a broad range of host organisms. For successful infection, Bordetella controls expression of four distinct classes of genes (referred to as class 1, 2, 3, and 4 genes) at distinct times in the infection cycle. This control is executed by a single two-component system, BvgAS. Interestingly, the transmembrane component of the two-component system, BvgS, consists of three phospho-transfer domains leading to phosphorylation of the response regulator, BvgA. Phosphorylated BvgA then controls expression of virulence genes and also controls bvgAS transcription. In this work, we perform simulations to characterize the role of the network architecture in governing gene expression in Bordetella. Our results show that the wild-type network is locally optimal for controlling the timing of expression of the different classes of genes involved in infection. In addition, the interplay between environmental signals and positive feedback aids the bacterium identify precise conditions for and control expression of virulence genes.
Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, Maharashtra, India. saini@che.iitb.ac.in.
Mahendra Kumar
MK
Prajapat
Supreet
S
Saini
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001884:Bordetella / Q000472:pathogenicity / Q000502:physiology*; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
D001426:Bacterial Proteins; D037521:Virulence Factors