“I will strive to foster an environment that allows free and open exchange of ideas and is conducive to the growth of the new students and postdoctoral fellows as successful and independent scientists. I will attempt to expose them to a combination of the established and newly emerging hypotheses and techniques, thereby promoting to their intellectual and scientific development.” Transcriptional Regulation and Functional Genomics of Host-Pathogen Interactions
Our research program utilizes an integrated approach to investigate the mechanism and importance of differential gene expression and the roles of newly identified factors in Bordetella pathogenesis. Bordetella species are small aerobic, gram-negative bacteria that colonize the respiratory tracts of humans and other animals. B. pertussis, the human pathogen results in the disease known as Whooping cough while B. bronchiseptica mainly infects animals and causes a variety of respiratory diseases. The bvgAS locus coordinately regulates the majority of the known products involved in Bordetella pathogenesis. As opposed to the traditional view of mediating a biphasic transition, the Bvg-regulatory system appears to control an entire spectrum of distinct gene expression states e.g. the Bvg+, Bvgi and the Bvg- phases. We are interested in understanding the molecular basis of transcriptional control by the facultative regulatory protein BvgA. One of the projects in the laboratory involves analyses of regulatory intricacies of expression of bipA, the first identified Bvgi–phase specific gene. The signal-dependent regulatory profile of bipA is determined by the interplay of transcriptional activation and repression. Expression of bipA in response to modulating signals is unusual in that this gene is most highly expressed at a point along the Bvg-regulatory continuum where the activity and the level of BvgA-P is predicted to be at an intermediate level. Experiments are also underway to determine the functional role of BipA in Bordetella pathogenesis. Another project in the laboratory takes advantage of the emerging field of functional genomics to identify new vaccine candidates and virulence factors and to study species-specific differences among Bordetella. We have identified a number of ORFs which have homology to several proteins that are known to play a role in virulence of other bacteria including outer membrane proteins and proteins involved in colonization. The gamut of genes will be characterized for their precise role in infection and persistence in the upper respiratory tract. Recently, we have demonstrated that the BvgAS locus positively regulates biofilm development in the three Bordetella species. We have also shown that these biofilms are highly tolerant to a number of antimicrobials including the ones that are currently recommended for treatment of both veterinary and human infections caused by Bordetella. Biofilms are structured communities of sessile bacterial cells that are encased in a self-produced polymeric organic matrix. The biofilm mode of existence is believed to contribute significantly to the pathogenesis of a number of bacterial infections. Presently, we are in the process of identifying Bvg-regulated factors that may be involved in biofilm formation. |
Recent Publications (selected):
Lopez-Boado, Y. S., Cobb, L. and Deora, R. Bordetella Flagellin is a Pro-inflammatory Determinant for Airway Epithelial Cells. 2005. Infect. Immun. In press Mishra, M., and Deora R. Mode of Action of the Bordetella BvgA Protein: Transcriptional Activation and Repression of the B. bronchiseptica bipA Promoter. 2005. J. Bacteriol. 187:6290-6299. Meenu Mishra, Gina Parise, Kara D. Jackson, Daniel J. Wozniak and Deora R. The BvgAS signal transduction system regulates biofilm development in Bordetella. 2005. J. Bacteriol. 187:1474-1484. Shuling Guo, Gregory Z. Ferl, Deora, R. Mireille Reidinger, Sheng Yin, Jim Kervin, Joseph A. Loo and Owen Witte. 2004. Proc. Natl Acad. Sci. A tyrosine phosphorylation site in Btk selectively regulates the efficiency of B cell calcium signaling by altering PLCgamma activation. Proc. Natl. Acad. Sci. U S A: 2004, 101:14180-5. Dulatov S, Hodes A, Dai L, Mandhana N, Liu M,Deora R, Simons RW, Zimmerly S and Miller JF. Tropism Switching in Bordetella phage defines a family of diversity-generating retroelements. 2004. Nature: 431:476-81. Deora R. Multiple mechanisms of bipA gene regulation by the Bordetella BvgAS phosphorelay system. 2004. Trends Microbiol.: 12: 63-65. Deora R. Differential regulation of Bordetella bipA gene: Distinct roles for different BvgA binding sites. 2002. J. Bacteriol. 184: 6942-6951. M. Liu, Deora, R., S. R. Doulatov, M. Gingery, F. A. Eiserling, A. Preston, D. J. Maskell, R. W. Simons, P. A. Cotter, J. Parkhill, and J. F. Miller. Reverse Transcriptase‑Mediated Tropism Switching in Bordetella Bacteriophage. 2002. Science. 295:2091‑2094. Deora R., Bootsma HJ, Miller JF, Cotter PA. Diversity in the Bordetella virulence regulon: transcriptional control of a Bvg‑intermediate phase gene. 2001 Mol. Microbiol. 40:669‑683. |