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Lakshmi Rajagopal, PhD

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Lakshmi Rajagopal, PhD

Infectious Disease

Academic Title: Associate Professor

Research Center: Center for Global Infectious Disease Research

Overview

Medical/Professional School
Jawaharla Nehru University, New Delhi
Bangalore Medical College, Karnataka
Fellowship
University of Washington, Seattle
Research Description

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.

GBS is a Gram-positive bacteria that causes invasive infections in human newborns and certain adult populations. Our studies on GBS focus on elucidating the role of a serine/threonine kinase in regulation of adaptive responses and virulence of the organism. We have shown that a serine/threonine kinase called Stk1 regulates de novo purine biosynthesis and toxin expression and is important for virulence of GBS.

In recent studies, we have shown that phosphorylation of the two-component regulator CovR by Stk1 eliminates CovR regulation of the GBS toxins. Current studies are focused toward identifying extracellular signals that dictate toxin expression of GBS (Lin, et al., Mol Microbiol 2009;71:1477-1495.

Like GBS, S. aureus is also Gram-positive cocci that can cause severe invasive disease in humans. We have recently begun to explore the role of a serine/threonine kinase homolog in virulence of S. aureus.

Lab URL

http://www.seattlechildrens.org/research/global-infectious-disease-research/rajagopal-lab/

Research Focus Area

Infectious Disease

Publications

Group B streptococcal infection of the choriodecidua induces dysfunction of the cytokeratin network in amniotic epithelium: a pathway to membrane weakening.
PLoS pathogens , 2014 Mar: 10(3)e1003920
Group B Streptococcus CovR regulation modulates host immune signalling pathways to promote vaginal colonization.
Cellular microbiology , July 2013: 15(7)1154-67
A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta.
The Journal of experimental medicine , June 2013: 210(6)1265-81
Vaccination with a UV-irradiated genetically attenuated mutant of Staphylococcus aureus provides protection against subsequent systemic infection.
The Journal of infectious diseases , Dec. 2012: 206(11)1734-44
Regulation of prokaryotic gene expression by eukaryotic-like enzymes.
Current opinion in microbiology , April 2012: 15(2)125-31
Serine/threonine phosphatase Stp1 mediates post-transcriptional regulation of hemolysin, autolysis, and virulence of group B Streptococcus.
The Journal of biological chemistry , Dec. 2011: 286(51)44197-210
Structure and substrate recognition of the Staphylococcus aureus protein tyrosine phosphatase PtpA.
Journal of molecular biology , Oct. 2011: 413(1)24-31
Aspects of eukaryotic-like signaling in Gram-positive cocci: a focus on virulence.
Future microbiology , July 2011: 6(7)747-61
Two paediatric cases of skin and soft-tissue infections due to clindamycin-resistant Staphylococcus aureus carrying a plasmid-encoded vga(A) allelic variant for a putative efflux pump.
International journal of antimicrobial agents , July 2011: 38(1)81-3
Regulation of CovR expression in Group B Streptococcus impacts blood-brain barrier penetration.
Molecular microbiology , July 2010: 77(2)431-43
Regulation of hemolysin expression and virulence of Staphylococcus aureus by a serine/threonine kinase and phosphatase.
PloS one , June 2010: 5(6)e11071
Identification of serine/threonine kinase substrates in the human pathogen group B streptococcus.
Journal of proteome research , May 2009: 8(5)2563-74
Understanding the regulation of Group B Streptococcal virulence factors.
Future microbiology , March 2009: 4(2)201-21
Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR.
Molecular microbiology , March 2009: 71(6)1477-95
Structure of the Streptococcus agalactiae family II inorganic pyrophosphatase at 2.80 A resolution.
Acta crystallographica. Section D, Biological crystallography , June 2007: 63(Pt 6)738-43
Structure of Streptococcus agalactiae serine/threonine phosphatase. The subdomain conformation is coupled to the binding of a third metal ion.
The FEBS journal , June 2007: 274(12)3128-37
Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae.
Molecular microbiology , Nov. 2006: 62(4)941-57
Crystallization and preliminary crystallographic analysis of two Streptococcus agalactiae proteins: the family II inorganic pyrophosphatase and the serine/threonine phosphatase.
Acta crystallographica. Section F, Structural biology and crystallization communications , Sept. 2006: 62(Pt 9)891-4
Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae.
Molecular microbiology , June 2005: 56(5)1329-46
MtaR, a regulator of methionine transport, is critical for survival of group B streptococcus in vivo.
Journal of bacteriology , Nov. 2003: 185(22)6592-9
A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence.
The Journal of biological chemistry , April 2003: 278(16)14429-41
Genetic locus encoding functions involved in biosynthesis and outer membrane localization of xanthomonadin in Xanthomonas oryzae pv. oryzae.
Journal of bacteriology , July 2002: 184(13)3539-48
US PATENT: Bacterial mutant BX065 and a method thereof (Shikimate dehydrogenase as a target for developing novel bactericides against plant pathogens)
Patent Number: 68,69,601. 3/22/2005. ,
US PATENT: Kinase inhibitors capable of increasing the sensitivity of bacterial pathogens to -lactam antibiotics
PCT/US2012/050635. 8/13/2012 ,

Presentations

Presentations TitleEventLocationDate
Rajagopal L, Clancy A and Rubens CE. A novel serine/threonine kinase essential for cell growth and division in Group B Streptococci, presented at the 6th Streptococcal Genetics Meeting. Asheville, NC. April 13-17, 2002.
Burnside K, Jewell K, Connelly JE and Rajagopal L. Role of a serine/threonine kinase in virulence of Staphylococcus aureus, presented at the 5th International Conference on Gram-Positive Microorganisms. San Diego, CA. June 14-18, 2009.
Lembo A, Gurney MA, Burnside K, Connelly JE, Doran KS and Rajagopal L. The two component system RgfC/A regulates CspA expression and Group B Streptococcal virulence, presented at the International Conference on Gram-Positive Microorganisms. Omaha, NE. October 10-13, 2010.
Whidbey C, Harrell M, Adams-Waldorf K and Rajagopal L. Penetration of human placenta by Group B Streptococci, presented at the International Conference for Gram-Positive Pathogens. Omaha, NE. October 7-10, 2012.
Whidbey C, Harrell M, Adams-Waldorf K and Rajagopal L. Penetration of human placenta by Group B Streptococci, presented at the Northwest Branch Meeting of the American Society for Microbiology. Seattle, WA. November 9-10, 2012.
Whidbey C, Ngo L, Adams Waldorf K and Rajagopal L. A mouse model of Group B Streptococcal associated preterm birth. 17th International Conference on Gram-Positive Microorganisms and 17th International Conference on Bacilli, Montecatini Terme, Italy, June 23-27, 2013.
Bierle CJ, Adams-Waldorf KM and Rajagopal L. Nonhuman primate and ex vivo models of intra-amniotic bacterial infection. Northwest Branch Meeting of the American Society for Microbiology. Seattle, Washington, November 15-16, 2013.
Adams Waldorf KM, Sooranna SR, Gravett MG, Paolella L, Gough M, Ngo L, Bammler T, MacDonald JW, Farin FM, Rajagopal L and Johnson MR. Acute Uterine Stretch Induces an Inflammatory "Pulse" in Amniotic Fluid and Maternal Plasma Followed by Preterm Labor in Nonhuman Primates. Society for Gynecologic Investigation, Florence, Italy, March 28, 2014.

Research Funding

Grant TitleGrantorAmountAward Date
Role of an ornithine rhamnolipid pigment in GBS virulenceNIH/NIAID (PI) $, $250,000 annual direct costsJuly 1, 2014 - June 30, 2019
Environmental signals that regulate GBS virulenceNIH/NIAID (PI) $150,000 annual direct costsSept. 1, 2013 - Aug. 31, 2015
Eukaryotic-type signaling mediates two-component regulation of GBS virulenceNIH/NIAID (PI) $247,362 annual direct costsJune 11, 2013 - May 31, 2014
GBS mediated in utero fetal injuryNIH/NIAID (Co-PI with Kristina Adams Waldorf) $, $499,906 annual direct costsJuly 1, 2012 - June 30, 2017

Primary Office

Seattle Children's Research Institute
JMB - 8 - Infectious Disease
1900 - 9th Ave
Seattle, WA 98101
206-884-7336

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