Our research is focused on two questions:
(1) How are some pathogens able to cause persistent infections, despite induction of an immune response? We are using the bacterial pathogen Brucella abortus to study this topic. B. abortus causes a febrile illness in humans, and if inappropriately treated, bacteria can persist for years in tissues such as liver, spleen and bone marrow. We are currently studying a virulence factor called the Type IV secretion system that allows Brucella to survive intracelllularly in tissues of the reticuloendothelial system by injecting proteins into infected macrophages. Our laboratory uses bacterial genetics and molecular biology techniques to characterize the function of the Type IV secretion system in Brucella. We are using macrophage and animal models and immunological techniques to dissect the interactions between the bacterium and host cells. By defining molecular interactions between bacteria and host cells, we will also learn how these interactions can be disrupted to develop better vaccines and treatments for chronic bacterial infections.
(2) How does malaria affect the mucosal barrier to infection? The most frequent presentation of disease from nontyphoidal Salmonella serotypes (NTS) in developed countries such as the US is gastroenteritis, a localized infection with low mortality. In contrast, immunocompromised individuals are at risk of developing NTS bacteremia, which can lead to serious sequelae, including meningitis, osteomyelitis, and septic shock. While these complications are infrequent in developed countries, NTS serotypes have become a leading cause of bacteremia in sub-Saharan Africa. An important risk factor for children to develop invasive NTS infections is malaria. Together with Dr. Luckhart’s lab here in the Medical Microbiology department, we have developed a mouse model to study the effects of malaria on the mucosal barrier to invasive infection.
2010. Roux CM, Butler, BP, Chau, J.Y., Paixão TA, Cheung, KW, Santos RL,, Luckhart S, Tsolis RM. Both hemolytic anemia and malaria parasite-specific factors increase susceptibility to non-typhoidal Salmonella infection in mice. Infect Immun., in press.
2009. Paixão TA, Roux CM, den Hartigh AB, Sankaran-Walters S, Dandekar S, Santos RL, Tsolis RM. Establishment of systemic Brucella melitensis infection through the digestive tract requires urease, the type IV secretion system, and lipopolysaccharide O-antigen. Infect Immun. 77:4197. PMID: 19651862
2009. Rolán HG, Xavier MN, Santos RL, Tsolis RM. Natural antibody contributes to host defense against an attenuated Brucella abortus virB mutant. Infect Immun. 2009 Jul;77(7):3004-13. PMID: 19364836
2009. Tsolis, R.M., R. Seshadri, R.L. Santos, F.J. Sangari, J.M. García Lobo, M.F. de Jong, Q. Ren, G. Myers, L.M. Brinkac, W.C. Nelson, R.T. DeBoy, S. Angiuoli, H. Khouri, G. Dimitrov, J.R. Robinson, S. Mulligan, R.L. Walker, P.E. Elzer, K.A. Hassan, I. T. Paulsen. Genome Degradation in Brucella ovis Corresponds with Narrowing of Its Host Range and Tissue Tropism. PLoS ONE 4(5): e5519. PMID 19436743
2009. A.R. Wattam., K. Williams, E. E. Snyder, N. F. Almeida, M. Shukla, J. Gillespie, O. Crasta, R. Kenyon, J. Lu, J. Shallom, R. Will, H. Yoo, T. Ficht, R.M. Tsolis, C. Munk, R. Tapia, C. Han, J.C. Detter, D. Bruce, T.S. Brettin, B. W. Sobral, S.M. Boyle, J. C. Setubal. Analysis of ten Brucella genomes reveals evidence for horizontal gene transfer despite a preferred intracellular lifestyle. J. Bacteriol. 191:3569-3579. PMID: 19346311
2009. Godinez, I., Raffatellu, M., Chu, H., Paixão, T.A., Haneda, T., Santos, R.L., Bevins, C.L., Tsolis, R.M., and A.J. Baumler. IL-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. Infect. Immun. 77:387-398. PMID: 18955477
2009. Raffatellu, M., M.D. George, Y. Akiyama, M.J. Hornsby, S.-P. Nuccio, T.A. Paixao, B.P. Butler, H. Chu, R.L. Santos, T. Berger, T.W. Mak, R.M. Tsolis, C.L. Bevins, J.V. Solnick, S. Dandekar and A.J. Baumler. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5:476-86. PMID: 19454351
2009. Costa E.A., M.R. Bomfim, F.G. da Fonseca, B.P. Drumond, F.M. Coelho, A.C. Vasconcelos, R. Furtini, T.A. Paixão, R.M. Tsolis, R.L. Santos, M. Resende. Ovine herpesvirus-2 infection in Foal, Brazil. Emerg Infect Dis. 15:844-5. PMID: 19402994
2008. de Jong, M.F., Y.-H. Sun, A.B. den Hartigh, J.M. van Dijl, R.M. Tsolis. Identification of VceA and VceC, two members of the VjbR regulon that are translocated into macrophages by the Brucella Type IV secretion system, Molecular Microbiology 70:1378-1396. PMID: 19019140
2008. den Hartigh, A.B., H.G. Rolán, M.F. de Jong, and R.M. Tsolis. VirB3 to VirB6 and VirB8 to VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system. J. Bacteriol. 190:4427-4436. PMID: 18469100
2008. Rolán, H.G. and R.M. Tsolis. 2008. Inactivation of the Type IV secretion system reduces the Th1 polarization of the immune response to Brucella abortus infection. Infect. Immun. 76:2008-2017. PMID: 18458071
2008. Rolán, H.G., A.B. den Hartigh, M. Kahl-McDonagh, T.A. Ficht, L.G. Adams and R.M. Tsolis. VirB12 is a serological marker of Brucella infection in experimental and natural hosts. Clin. Vaccine Immunol. 15208-214.
2008. Carvalho Neta, A.V., A.P.R. Steynen, T.A. Paixão, K.L. Miranda, F.L. Silva, C.M. Roux, R.M. Tsolis, H.A. Lewin, L.G. Adams, A.F. Carvalho, A.P. Lage, and R.L. Santos. Modulation of trophoblastic immune response by Brucella abortus. Infect. Immun. 76: 1897-1907. PMID: 18316388
2008. Godinez, I., T. Haneda, M. Raffatellu, M.D. George, T.A. Paixão, H.G. Rolán, R.L. Santos, S. Dandekar, R.M. Tsolis and A.J. Bäumler. T cells help to amplify inflammatory responses induced by Salmonella enterica serotype Typhimurium in the intestinal mucosa. Infect. Immun, 76:2008-2017. PMID: 18347048
2008. Lightfield, K.L., J. Persson, S.W. Brubaker, C.E. Witte, J. von Moltke, E.A. Dunipace, T. Henry, Y.-H. Sun, D. Cado, W.F. Dietrich, D.M. Monack, R.M. Tsolis, and R.E. Vance. Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nature Immunology, 9:1171-8. PMID: 18724372
2007. Roux, C.M., Rolan, H.G., Santos, R.L., Beremand, P.D., Thomas, T.L., Adams, L.G. and R.M. Tsolis. Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice. Cell. Microbiol, 9:1851-69. PMID: 17441987
2007. Rolán, H.G. and R. M. Tsolis. Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization. Infect. Immun. 75: 2965-73. PMID: 17420243
2007. Sun, Y.-H., H.G. Rolán and R.M. Tsolis. Injection of flagellin into the host cell cytosol by Salmonella enterica serotype Typhimurium. J. Biol. Chem. 282:33897-901. PMID: 17911114
Teaching and Research Awards