Lakshmi Rajagopal, PhD

Lakshmi  Rajagopal,  PhD

Academic Title: Professor

"Hearing from families that lost their babies to group B streptococcus infection motivates me to search for better ways to fight these bacteria."

  • Biography

    Lakshmi Rajagopal, PhD: Professor of Pediatric Infectious Diseases and Microbiology. 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.

    For more information, please visit Rajagopal Lab.

    • Related Resources

    • Related Pages

    • Rajagopal Lab

      The Rajagopal Lab utilizes genetic, molecular, biochemical and proteomic approaches to study infectious diseases caused by bacteria. The lab focuses on the human pathogens group B Streptococcus and Staphylococcus aureus. Research areas of focus include bacteriology, specifically bacterial pathogenesis, bacterial virule

  • Patient Testimonials

  • Publications

    Manuscripts in Refereed Journals

    • Armistead B, Herrero-Foncubierta P, Coleman M, Quach P, Whidbey C, Justicia J, Tapia R, Casares R, Millán A, Haidour A, Granger JR, Vornhagen J, Santana-Ufret V, Merillat S, Adams Waldorf K, Cuerva JM, Rajagopal L
      Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection.
      32198389 Nature communications, 2020 Mar 20 : 11(1)1502 PMCID:PMC7083881
    • Armistead B, Whidbey C, Iyer LM, Herrero-Foncubierta P, Quach P, Haidour A, Aravind L, Cuerva JM, Jaspan HB, Rajagopal L
      Corrigendum: The cyl Genes Reveal the Biosynthetic and Evolutionary Origins of the Group B Streptococcus Hemolytic Lipid, Granadaene.
      32161580 Frontiers in microbiology, 2020 : 11325 PMCID:PMC7052477
    • Robbiani DF, Olsen PC, Costa F, Wang Q, Oliveira TY, Nery N Jr, Aromolaran A, do Rosário MS, Sacramento GA, Cruz JS, Khouri R, Wunder EA Jr, Mattos A, de Paula Freitas B, Sarno M, Archanjo G, Daltro D, Carvalho GBS, Pimentel K, de Siqueira IC, de Almeida JRM, Henriques DF, Lima JA, Vasconcelos PFC, Schaefer-Babajew D, Azzopardi SA, Bozzacco L, Gazumyan A, Belfort R Jr, Alcântara AP, Carvalho G, Moreira L, Araujo K, Reis MG, Keesler RI, Coffey LL, Tisoncik-Go J, Gale M Jr, Rajagopal L, Adams Waldorf KM, Dudley DM, Simmons HA, Mejia A, O'Connor DH, Steinbach RJ, Haese N, Smith J, Lewis A, Colgin L, Roberts V, Frias A, Kelleher M, Hirsch A, Streblow DN, Rice CM, MacDonald MR, de Almeida ARP, Van Rompay KKA, Ko AI, Nussenzweig MC
      Risk of Zika microcephaly correlates with features of maternal antibodies.
      31413072 The Journal of experimental medicine, 2019 Aug 14
    • Armistead B, Oler E, Adams Waldorf K, Rajagopal L
      The Double Life of Group B Streptococcus: Asymptomatic Colonizer and Potent Pathogen.
      30711542 Journal of molecular biology, 2019 Jul 26 : 431(16)2914-2931 PMCID:PMC6646060
    • Al-Haddad BJS, Oler E, Armistead B, Elsayed NA, Weinberger DR, Bernier R, Burd I, Kapur R, Jacobsson B, Wang C, Mysorekar I, Rajagopal L, Adams Waldorf KM
      The fetal origins of mental illness.
      31207234 American journal of obstetrics and gynecology, 2019 Jun 15
    • Al-Haddad BJS, Jacobsson B, Chabra S, Modzelewska D, Olson EM, Bernier R, Enquobahrie DA, Hagberg H, Östling S, Rajagopal L, Adams Waldorf KM, Sengpiel V
      Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.
      30840048 JAMA psychiatry, 2019 Jun 1 : 76(6)594-602 PMCID:PMC6551852
    • Walker CL, Little ME, Roby JA, Armistead B, Gale M Jr, Rajagopal L, Nelson BR, Ehinger N, Mason B, Nayeri U, Curry CL, Adams Waldorf KM
      Zika virus and the nonmicrocephalic fetus: why we should still worry.
      30171843 American journal of obstetrics and gynecology, 2019 Jan. : 220(1)45-56 PMCID:PMC6501788
    • Adams Waldorf KM, Olson EM, Nelson BR, Little ME, Rajagopal L
      The Aftermath of Zika: Need for Long-Term Monitoring of Exposed Children.
      29960747 Trends in microbiology, 2018 Sept. : 26(9)729-732 PMCID:PMC6136144
    • Dudley DM, Van Rompay KK, Coffey LL, Ardeshir A, Keesler RI, Bliss-Moreau E, Grigsby PL, Steinbach RJ, Hirsch AJ, MacAllister RP, Pecoraro HL, Colgin LM, Hodge T, Streblow DN, Tardif S, Patterson JL, Tamhankar M, Seferovic M, Aagaard KM, Martín CS, Chiu CY, Panganiban AT, Veazey RS, Wang X, Maness NJ, Gilbert MH, Bohm RP, Adams Waldorf KM, Gale M Jr, Rajagopal L, Hotchkiss CE, Mohr EL, Capuano SV 3rd, Simmons HA, Mejia A, Friedrich TC, Golos TG, O'Connor DH
      Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.
      29967348 Nature medicine, 2018 Aug. : 24(8)1104-1107 PMCID:PMC6082723
    • Walker CL, Merriam AA, Ohuma EO, Dighe MK, Gale M Jr, Rajagopal L, Papageorghiou AT, Gyamfi-Bannerman C, Adams Waldorf KM
      Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection.
      29738748 American journal of obstetrics and gynecology, 2018 Aug. : 219(2)187.e1-187.e20 PMCID:PMC6066422
    • Vornhagen J, Armistead B, Santana-Ufret V, Gendrin C, Merillat S, Coleman M, Quach P, Boldenow E, Alishetti V, Leonhard-Melief C, Ngo LY, Whidbey C, Doran KS, Curtis C, Waldorf KMA, Nance E, Rajagopal L
      Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection.
      29629904 The Journal of clinical investigation, 2018 Apr 9
    • Mitchell T, MacDonald JW, Srinouanpranchanh S, Bammler TK, Merillat S, Boldenow E, Coleman M, Agnew K, Baldessari A, Stencel-Baerenwald JE, Tisoncik-Go J, Green RR, Gale MJ Jr., Rajagopal L, Adams Waldorf KM
      Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.
      29475580 American journal of obstetrics and gynecology, 2018 April : 218(4)438.e1-438.e16
    • Gendrin C, Merillat S, Vornhagen J, Coleman M, Armistead B, Ngo L, Aggarwal A, Quach P, Berrigan J, Rajagopal L
      Diminished Capsule Exacerbates Virulence, Blood-Brain Barrier Penetration, Intracellular Persistence, and Antibiotic Evasion of Hyperhemolytic Group B Streptococci.
      29301010 The Journal of infectious diseases, 2018 Mar 13 : 217(7)1128-1138
    • Lannon SMR, Adams Waldorf KM, Fiedler T, Kapur RP, Agnew K, Rajagopal L, Gravett MG, Fredricks DN
      Parallel detection of lactobacillus and bacterial vaginosis-associated bacterial DNA in the chorioamnion and vagina of pregnant women at term.
      29478370 The journal of maternal-fetal and neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2018 Mar 12 : 1-9
    • Gendrin C, Vornhagen J, Armistead B, Singh P, Whidbey C, Merillat S, Knupp D, Parker R, Rogers LM, Quach P, Iyer LM, Aravind L, Manning SD, Aronoff DM, Rajagopal L
      A Nonhemolytic Group B Streptococcus Strain Exhibits Hypervirulence.
      29244079 The Journal of infectious diseases, 2018 Mar 5 : 217(6)983-987 PMCID:PMC5853813
    • Adams Waldorf KM, Nelson BR, Stencel-Baerenwald JE, Studholme C, Kapur RP, Armistead B, Walker CL, Merillat S, Vornhagen J, Tisoncik-Go J, Baldessari A, Coleman M, Dighe MK, Shaw DWW, Roby JA, Santana-Ufret V, Boldenow E, Li J, Gao X, Davis MA, Swanstrom JA, Jensen K, Widman DG, Baric RS, Medwid JT, Hanley KA, Ogle J, Gough GM, Lee W, English C, Durning WM, Thiel J, Gatenby C, Dewey EC, Fairgrieve MR, Hodge RD, Grant RF, Kuller L, Dobyns WB, Hevner RF, Gale M Jr, Rajagopal L
      Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.
      29400709 Nature medicine, 2018 March : 24(3)368-374 PMCID:PMC5839998
    • Vornhagen J, Quach P, Santana-Ufret V, Alishetti V, Brokaw A, Armistead B, Qing Tang H, MacDonald JW, Bammler TK, Adams Waldorf KM, Uldbjerg N, Rajagopal L
      Human cervical mucus plugs exhibit insufficiencies in antimicrobial activity towards Group B Streptococcus.
      29425317 The Journal of infectious diseases, 2018 Feb 7
    • Vornhagen J, Adams Waldorf KM, Rajagopal L
      Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies.
      28633864 Trends in microbiology, 2017 Nov. : 25(11)919-931 PMCID:PMC5650539
    • Gendrin C, Shubin NJ, Boldenow E, Merillat S, Clauson M, Power D, Doran KS, Abrink M, Pejler G, Rajagopal L, Piliponsky AM
      Mast cell chymase decreases the severity of group B Streptococcus infections.
      28916188 The Journal of allergy and clinical immunology, 2017 Sep 12 : PMCID:PMC5847414
    • Harrell MI, Burnside K, Whidbey C, Vornhagen J, Adams Waldorf KM, Rajagopal L
      Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus Intrauterine Infection.
      29034376 Journal of infectious diseases and medicine, 2017 Sept. : 2(2) PMCID:PMC5635843
    • Li J, Baird MA, Davis MA, Tai W, Zweifel LS, Adams Waldorf KM, Gale M Jr, Rajagopal L, Pierce RH, Gao X
      Dramatic enhancement of the detection limits of bioassays via ultrafast deposition of polydopamine.
      29082104 Nature biomedical engineering, 2017 : 1 PMCID:PMC5654575
    • Adams Waldorf KM, Stencel-Baerenwald JE, Kapur RP, Studholme C, Boldenow E, Vornhagen J, Baldessari A, Dighe MK, Thiel J, Merillat S, Armistead B, Tisoncik-Go J, Green RR, Davis MA, Dewey EC, Fairgrieve MR, Gatenby JC, Richards T, Garden GA, Diamond MS, Juul SE, Grant RF, Kuller L, Shaw DW, Ogle J, Gough GM, Lee W, English C, Hevner RF, Dobyns WB, Gale M Jr, Rajagopal L
      Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate.
      27618651 Nature medicine, 2016 Nov. : 22(11)1256-1259
    • Boldenow E, Gendrin C, Ngo L, Bierle C, Vornhagen J, Coleman M, Merillat S, Armistead B, Whidbey C, Alishetti V, Santana-Ufret V, Ogle J, Gough M, Srinouanprachanh S, MacDonald JW, Bammler TK, Bansal A, Liggitt HD, Rajagopal L, Waldorf KM
      GROUP B STREPTOCOCCUS CIRCUMVENTS NEUTROPHILS AND NEUTROPHIL EXTRACELLULAR TRAPS DURING AMNIOTIC CAVITY INVASION AND PRETERM LABOR.
      27819066 Science immunology, 2016 Oct. : 1(4) PMCID:PMC5089172
    • Vornhagen J, Quach P, Boldenow E, Merillat S, Whidbey C, Ngo LY, Adams Waldorf KM, Rajagopal L
      Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth.
      27353757 mBio, 2016 Jun 28 : 7(3) PMCID:PMC4937215
    • Adams Waldorf KM, Singh N, Mohan AR, Young RC, Ngo L, Das A, Tsai J, Bansal A, Paolella L, Herbert BR, Sooranna SR, Gough GM, Astley C, Vogel K, Baldessari AE, Bammler TK, MacDonald J, Gravett MG, Rajagopal L, Johnson MR
      Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates.
      26284599 American journal of obstetrics and gynecology, 2015 Dec. : 213(6)830.e1-830.e19 PMCID:PMC4679421
    • Vornhagen J, Burnside K, Whidbey C, Berry J, Qin X, Rajagopal L
      Kinase Inhibitors that Increase the Sensitivity of Methicillin Resistant Staphylococcus aureus to β-Lactam Antibiotics.
      26506394 Pathogens (Basel, Switzerland), 2015 Oct 22 : 4(4)708-21 PMCID:PMC4693160
    • McAdams RM, Bierle CJ, Boldenow E, Weed S, Tsai J, Beyer RP, MacDonald JW, Bammler TK, Liggitt HD, Farin FM, Vanderhoeven J, Rajagopal L, Adams Waldorf KM
      Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina.
      26195546 Infection and immunity, 2015 Oct. : 83(10)3909-17 PMCID:PMC4567641
    • Gendrin C, Vornhagen J, Ngo L, Whidbey C, Boldenow E, Santana-Ufret V, Clauson M, Burnside K, Galloway DP, Waldorf KA, Piliponsky AM, Rajagopal L
      Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection.
      26425734 Science advances, 2015 Jul 17 : 1(6)e1400225 PMCID:PMC4584422
    • Whidbey C, Vornhagen J, Gendrin C, Boldenow E, Samson JM, Doering K, Ngo L, Ezekwe EA Jr, Gundlach JH, Elovitz MA, Liggitt D, Duncan JA, Adams Waldorf KM, Rajagopal L
      A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury.
      25750210 EMBO molecular medicine, 2015 Mar 6 : 7(4)488-505 PMCID:PMC4403049
    • Gendrin C, Lembo A, Whidbey C, Burnside K, Berry J, Ngo L, Banerjee A, Xue L, Arrington J, Doran KS, Tao WA, Rajagopal L
      The sensor histidine kinase RgfC affects group B streptococcal virulence factor expression independent of its response regulator RgfA.
      25561709 Infection and immunity, 2015 March : 83(3)1078-88 PMCID:PMC4333453
    • Whidbey C, Burnside K, Martinez RM, Gendrin C, Vornhagen J, Frando A, Harrell MI, McAdams R, Rajagopal L
      A Hyperhemolytic/Hyperpigmented Group B Streptococcus Strain with a CovR Mutation Isolated from an Adolescent Patient with Sore Throat.
      26913295 Clinical research in infectious diseases, 2015 : 2(2)1018-1022 PMCID:PMC4762654
    • Vanderhoeven JP, Bierle CJ, Kapur RP, McAdams RM, Beyer RP, Bammler TK, Farin FM, Bansal A, Spencer M, Deng M, Gravett MG, Rubens CE, Rajagopal L, Adams Waldorf KM
      Group B streptococcal infection of the choriodecidua induces dysfunction of the cytokeratin network in amniotic epithelium: a pathway to membrane weakening.
      24603861 PLoS pathogens, 2014 March : 10(3)e1003920 PMCID:PMC3946355
    • Patras KA, Wang NY, Fletcher EM, Cavaco CK, Jimenez A, Garg M, Fierer J, Sheen TR, Rajagopal L, Doran KS
      Group B Streptococcus CovR regulation modulates host immune signalling pathways to promote vaginal colonization.
      23298320 Cellular microbiology, 2013 July : 15(7)1154-67 PMCID:PMC3657335
    • Whidbey C, Harrell MI, Burnside K, Ngo L, Becraft AK, Iyer LM, Aravind L, Hitti J, Waldorf KM, Rajagopal L
      A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta.
      23712433 The Journal of experimental medicine, 2013 June : 210(6)1265-81 PMCID:PMC3674703
    • Burnside K, Lembo A, Harrell MI, Klein JA, Lopez-Guisa J, Siegesmund AM, Torgerson TR, Oukka M, Molina DM, Rajagopal L
      Vaccination with a UV-irradiated genetically attenuated mutant of Staphylococcus aureus provides protection against subsequent systemic infection.
      22966130 The Journal of infectious diseases, 2012 Dec. : 206(11)1734-44 PMCID:PMC3488195
    • Burnside K, Rajagopal L
      Regulation of prokaryotic gene expression by eukaryotic-like enzymes.
      22221896 Current opinion in microbiology, 2012 April : 15(2)125-31 PMCID:PMC3320669
    • Burnside K, Lembo A, Harrell MI, Gurney M, Xue L, BinhTran NT, Connelly JE, Jewell KA, Schmidt BZ, de los Reyes M, Tao WA, Doran KS, Rajagopal L
      Serine/threonine phosphatase Stp1 mediates post-transcriptional regulation of hemolysin, autolysis, and virulence of group B Streptococcus.
      22081606 The Journal of biological chemistry, 2011 Dec. : 286(51)44197-210 PMCID:PMC3243546
    • Vega C, Chou S, Engel K, Harrell ME, Rajagopal L, Grundner C
      Structure and substrate recognition of the Staphylococcus aureus protein tyrosine phosphatase PtpA.
      21871460 Journal of molecular biology, 2011 Oct. : 413(1)24-31 PMCID:PMC3204379
    • Qin X, Poon B, Kwong J, Niles D, Schmidt BZ, Rajagopal L, Gantt S
      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.
      21549571 International journal of antimicrobial agents, 2011 July : 38(1)81-3
    • Burnside K, Rajagopal L
      Aspects of eukaryotic-like signaling in Gram-positive cocci: a focus on virulence.
      21797690 Future microbiology, 2011 July : 6(7)747-61 PMCID:PMC3236639
    • Lembo A, Gurney MA, Burnside K, Banerjee A, de los Reyes M, Connelly JE, Lin WJ, Jewell KA, Vo A, Renken CW, Doran KS, Rajagopal L
      Regulation of CovR expression in Group B Streptococcus impacts blood-brain barrier penetration.
      20497331 Molecular microbiology, 2010 July : 77(2)431-43 PMCID:PMC2909351
    • Burnside K, Lembo A, de Los Reyes M, Iliuk A, Binhtran NT, Connelly JE, Lin WJ, Schmidt BZ, Richardson AR, Fang FC, Tao WA, Rajagopal L
      Regulation of hemolysin expression and virulence of Staphylococcus aureus by a serine/threonine kinase and phosphatase.
      20552019 PloS one, 2010 June : 5(6)e11071 PMCID:PMC2884019
    • Silvestroni A, Jewell KA, Lin WJ, Connelly JE, Ivancic MM, Tao WA, Rajagopal L
      Identification of serine/threonine kinase substrates in the human pathogen group B streptococcus.
      19309132 Journal of proteome research, 2009 May : 8(5)2563-74 PMCID:PMC2863997
    • Rajagopal L
      Understanding the regulation of Group B Streptococcal virulence factors.
      19257847 Future microbiology, 2009 March : 4(2)201-21 PMCID:PMC2691590
    • Lin WJ, Walthers D, Connelly JE, Burnside K, Jewell KA, Kenney LJ, Rajagopal L
      Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR.
      19170889 Molecular microbiology, 2009 March : 71(6)1477-95 PMCID:PMC3133594
    • Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A
      Structure of the Streptococcus agalactiae family II inorganic pyrophosphatase at 2.80 A resolution.
      17505113 Acta crystallographica. Section D, Biological crystallography, 2007 June : 63(Pt 6)738-43 PMCID:PMC2365889
    • Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A
      Structure of Streptococcus agalactiae serine/threonine phosphatase. The subdomain conformation is coupled to the binding of a third metal ion.
      17521332 The FEBS journal, 2007 June : 274(12)3128-37 PMCID:PMC2361094
    • Rajagopal L, Vo A, Silvestroni A, Rubens CE
      Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae.
      17005013 Molecular microbiology, 2006 Nov. : 62(4)941-57 PMCID:PMC2593684
    • Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A
      Crystallization and preliminary crystallographic analysis of two Streptococcus agalactiae proteins: the family II inorganic pyrophosphatase and the serine/threonine phosphatase.
      16946472 Acta crystallographica. Section F, Structural biology and crystallization communications, 2006 Sept. : 62(Pt 9)891-4 PMCID:PMC2242878
    • Rajagopal L, Vo A, Silvestroni A, Rubens CE
      Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae.
      15882424 Molecular microbiology, 2005 June : 56(5)1329-46 PMCID:PMC2366208
    • Shelver D, Rajagopal L, Harris TO, Rubens CE
      MtaR, a regulator of methionine transport, is critical for survival of group B streptococcus in vivo.
      14594832 Journal of bacteriology, 2003 Nov. : 185(22)6592-9 PMCID:PMC262094
    • Rajagopal L, Clancy A, Rubens CE
      A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence.
      12562757 The Journal of biological chemistry, 2003 April : 278(16)14429-41
    • Goel AK, Rajagopal L, Nagesh N, Sonti RV
      Genetic locus encoding functions involved in biosynthesis and outer membrane localization of xanthomonadin in Xanthomonas oryzae pv. oryzae.
      12057948 Journal of bacteriology, 2002 July : 184(13)3539-48 PMCID:PMC135150

    Other Publications

    • Lakshmi Rajagopal, Kellie Burnside Howard, Christopher Whidbey
      US PATENT: Kinase inhibitors capable of increasing the sensitivity of bacterial pathogens to -lactam antibiotics
      PCT/US2012/050635. 8/13/2012
    • Ajay Kumar Goel, Lakshmi Rajagopal, Ramesh V. Sonti
      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.
  • Presentations

    Presentation Title Event Location Date
    GBS virulence factors and Preterm Birth (Lecture) 3/2019: Society for Reproductive Investigation (SRI), GBS Mini-Symposium Paris, France March 2019
    Role of EMT and Epithelial Exfoliation on GBS infections (Lecture) 3/2019: Preterm Birth International Collaborative (PREBIC), Society for Reproductive Investigation (SRI), Satellite Symposium Paris, France March 2019
    Importance of polyenes to GBS hemolysis (Lecture) 8/2018: Gordon Research Conference Streptococcal Biology Sunday River, Maine Aug. 2018
    Role of cervical mucus plugs in GBS infection (Lecture) 2/2018: International Symposium on Streptococcus agalactiae Disease (ISSAD) Cape Town, South Africa Feb. 2018
    Mechanisms of ascending GBS infection (Lecture) 10/2017: 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017 Nadi, Fiji Oct. 2017
    The hemolytic pigment of Group B Streptococcus induces pore formation, pyroptosis, and infection-associated fetal injury and preterm birth (Lecture) 11/2014: XIX Lancefield International Symposium on Streptococci and Streptococcal Diseases Buenos Aires, Argentina Nov. 2014
    Mitchell TB, Bammler T, MacDonald J, Srinouanprachanh S, Ogle J, Gough M, Boldenow E, Ngo L, Rajagopal L, Adams Waldorf K. Fetal sepsis in utero induces disruption of gene networks involved in cardiac morphogenesis in a nonhuman primate model of infe Society for Reproductive Investigation Annual Meeting (Poster) Montreal, Canada
    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 Labo
    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.
    McCartney SA, Kapur R, Liggitt HD, Ngo L, Boldewow L, Rajagopal L, Adams Waldorf KM. Correlation between placental pathology and fetal injury in a unique non-human primate model of chorioamnionitis. 2015 Infectious Disease Soc Ob/Gyn.
    Adams Waldorf K, Boldenow E, Ngo L, Liggitt HD, Ogle J, Gough M, Bierle C, Rajagopal L. Production of -hemolysin by GBS Increases Risk of Preterm Labor, Microbial Invasion of the Amniotic Cavity and Fetal Injury. O-023; 2016 Society Reproductive Inve
    Armistead B, Vornhagen J, Boldenow E, Melendez M, Gendrin C, Merillat S, Rajagopal L. 2016. The Group B Streptococcus hemolytic toxin is cytolytic to T cells. 8th International Conference on Streptococcal Genetics; Washington, DC.
    Boldenow E, Gendrin C, Ngo L, Bierle C, Vornhagen J, Merillat S, Armistead B, Whidbey C, Alishetti V, Ogle J, Gough M, Liggitt H, Adams Waldorf K, Rajagopal L. 2016. Hyperhemolytic Group B Streptococcus impairs neutrophil function and increases prete
    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,
    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.
    Vornhagen J, Armistead B, Santana-Ufret V, Quatch P, Ngo L, Whidbey C, Rajagopal L. 2016. Group B Streptococcus induces epithelial exfoliation. 8th International Conference on Streptococcal Genetics; Washington, DC.
    Coleman MM* (poster), Armistead BE, Rajagopal L. Dendritic cells are susceptible to death in response to hyperpigmented GBS. 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017. Nadi, Fiji. 10/2017.
    Gendrin C, Vornhagen J, Ngo L, Whidbey C, Clauson M, Adams Waldorf K, Adrian M Piliponsky AM, Rajagopal L. Activation of mast cells by a hemolytic pigment prevents GBS colonization. XIX Lancefield International Symposium on Streptococci and Streptoco
    Armistead B* (poster), Whidbey C, Vornhagen J, Cuerva JM, Rajagopal L. Expression of the Group B Streptococcus cyl operon in Lactotoccus lactis confers hemolysin production. 20th Lancefield International Symposium on Streptococci and Streptococcal Di
    8/2019: How a commensal becomes a pathogen during pregnancy: a Jekyll and Hyde story of GBS (Lecture) IDSOG Annual Meeting Big Sky, Montana
    Vornhagen J, Santana-Ufret V, Quach P, Ngo L, Rajagopal L. Group B Streptococcus induction of epithelial to mesenchymal transition. UW-Kobe University Symposium on Cell Signaling, Seattle, WA, September 10-11, 2015.
    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.
    Montenegro-Burke R, Aronoff D, McLean J, Rajagopal L, Adams Waldorf K. Dynamic Changes in the Metabolic Signature of Amniotic Fluid during Infection-Associated Preterm Labor. 2016 Society Reproductive Investigation; Montreal, Canada; poster.
    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.
    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
    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.
    Vornhagen J, Santana-Ufret V, Whidbey C, Ngo L, Liggitt D, Piliponsky A, Rajagopal R. Role of Group B Streptococcus virulence factors during colonization and ascending infection. XIX Lancefield International Symposium on Streptococci and Streptococca
    Whidbey C, Boldenow E, Vornhagen J, Rajagopal L. Biochemical characterization of the ornithine rhamnolipid pigment of group B streptococcus and its interaction with host cells. XIX Lancefield International Symposium on Streptococci and Streptococcal
    Weed S, Liggitt HD, Johnson B, Tsai J, Beyer R, Bammler T, Boldenow E, Parker E, Vanderhoeven J, Bierle C, Rajagopal L, Adams Waldorf K. Epithelial-Mesenchymal Transition: A Novel Mechanism for Placental Membrane Weakening. O-142; 2016 Society Reprod
  • Research Funding

    Grant Title Grantor Amount Award Date
    Immune Control of Group B Streptococcal Placental - R01 AI145890 NIH/NIAID $716,039 annual direct costs Sep 1, 2019 - Aug 31, 2024
    JAK-STAT Control of Zika Virus-Induced Fetal Injury - R01 AI143265 NIH/UW $125,000 annual direct costs Jul 1, 2019 - Jun 30, 2024
    Role of the GBS hyaluronidase in regulation of immune responses during pregnancy - R01 AI33976 NIH/NIAID $150,000 annual direct costs Jun 22, 2017 - May 31, 2022
    Role of the GBS hyaluronidase in regulation of immune responses during pregnancy - R01 AI33976 NIH $659,671 annual direct costs Jun 22, 2017 - May 31, 2022
    Role of human cervical mucus plugs in ascending GBS infection - R21 AI125907 NIH/NIAID $161,212 annual direct costs Jun 24, 2016 - May 31, 2018
    Role of an ornithine rhamnolipid pigment in GBS virulence - R01 AI112619 NIH/NIAID $250,000 annual direct costs Jul 1, 2014 - Jun 30, 2019
    GBS mediated in utero fetal injury - R01 AI100989 NIH/NIAID Jul 1, 2012 - Jun 30, 2018

Overview

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.

Research Focus Area

Infectious Disease