Our research interest is to understand signaling events that occur during bacterial disease pathogenesis. The human pathogens that we study are Group B Streptococcus (GBS) and Staphylococcus aureus. Although both GBS and S. aureus are commensal organisms, these bacteria can also become disease-causing pathogens. GBS are commonly found in the recto-vaginal tract of healthy women but can cause severe invasive disease in human newborns and adults that include elderly, immunocompromised and diabetic individuals. Our studies on GBS are focused on understanding how these bacteria adapt to the environmental niches encountered during their life cycle. Studies from our research have shown that GBS encodes signaling factors such as a serine/threonine kinase; these proteins were previously thought only to exist in higher forms such as eukaryotic organisms. Our research showed that the kinase regulates the expression of the GBS toxin known as hemolysin/cytolysin and also enables the bacteria to adapt to nutrient starvation. In recent studies, we demonstrated that the kinase affects toxin expression based upon its interaction with a DNA-binding response regulator known as CovR. The interaction between the kinase and CovR represents novel findings in bacterial environmental adaptation. Current research is focused toward identifying the environmental cues/signals that are sensed by these bacteria for regulation of toxin expression and virulence. Like GBS, S. aureus are also Gram-positive bacteria that can cause severe invasive disease in humans. We have recently identified a number of novel genes/signaling factors that regulate toxin expression in S. aureus. Current studies are focused on elucidating how these signaling factors regulate toxin expression and S. aureus virulence. The ultimate goal is to use the information gathered from our research to identify novel compounds that can be used to treat these bacterial infections.
Bangalore University, India, B.Sc., Chemistry, Botany and Zoology, 1991
Graduate and Postgraduate
Madurai Kamaraj University, India, M.Sc., Biotechnology, 1993
Jawaharlal Nehru University, New Delhi, India, Ph.D., Life Sciences, 1999
University of Washington, Department of Microbiology, Postgraduate Fellowship, 1999-2000
Children's Hospital and Regional Medical Center/University of Washington, Department of Pediatrics, Postgraduate Fellowship, 2000-2004
Rajagopal, L., Clancy, A., and Rubens, C.E. (2003) A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence. J Biol Chem 278: 14429-14441.
Rajagopal, L., Vo, A., Silvestroni, A., and Rubens, C.E. (2005) Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae. Mol Microbiol 56: 1329-1346.
Rantanen, M.K., Lehtio, L., Rajagopal, L., Rubens, C.E., and Goldman, A. (2006) Crystallization and preliminary crystallographic analysis of two Streptococcus agalactiae proteins: the family II inorganic pyrophosphatase and the serine/threonine phosphatase. Acta Crystallograph Sect F Struct Biol Cryst Commun 62: 891-894.
Rajagopal, L., Vo, A., Silvestroni, A., and Rubens, C.E. (2006) "Regulation of cytotoxin expression by converging eukaryotic-type and two component signalling mechanisms in Streptococcus agalactiae" Mol Microbiol 62: 941-57