Andreas J. Bäumler, Ph.D.
Professor and Vice Chair of Research
University of California, Davis
One Shields Avenue
Genome and Biomedical Sciences Facility
Davis, California 95616
Tel: (530) 754-7225
Lab: (530) 754-8534
Fax: (530) 754-7240
Ebehard-Karls Universität, Tübingen, Germany, B.S. Microbiology
Ebehard-Karls Universität, Tübingen, Germany, Ph.D. Microbiology
Oregon Health Sciences University, Portland, Oregon, Post-Doc Microbiology
Graduate Group Membership
Molecular Mechanisms of Salmonella Interaction with the Intestinal Mucosa
The genus Salmonella contains a group of closely related organisms that are pathogenic for humans and other vertebrates. The human disease manifestations associated most frequently with Salmonella serotypes are typhoid fever caused by Salmonella typhi and gastroenteritis caused by non-typhoidal Salmonella serotypes (e.g. S. typhimurium). One focus of my lab is to understand why typhoid fever and gastroenteritis differ in the host response elicited at the site where both infections originate, the intestinal mucosa. Gastroenteritis is a typical diarrheal disease characterized by a massive neutrophil influx in the terminal ileum and colon. We study S. typhimurium virulence factors (i.e. two type III secretion systems) and host factors (i.e. Toll-like receptors, Nod-like receptors, complement and key cytokines) involved in orchestrating this acute intestinal inflammatory reaction. In contrast to gastroenteritis, typhoid fever caused by S. typhi is not a diarrheal disease and intestinal inflammatory infiltrates are dominated by mononuclear cells (i.e. macrophages and dendritic cells), while neutrophils are scarce. The ability to prevent neutrophil infiltration and to evade innate immunity is encoded by a S. typhi specific DNA region, the viaB locus. We are studying the molecular mechanisms by which the virulence factors encoded within the viaB locus alters the host response to infection using a variety of in vivo and tissue culture models.
More recently we have become interested in the fact that infection with human immune deficiency virus (HIV) alters the course of S. typhimurium infection in humans. Unlike immunocompetent individuals, which develop gastroenteritis, S. typhimurium infection manifests as a life threatening bacteremia in HIV patients. Due to the current HIV epidemic, infections with non-typhoidal Salmonella serotypes, such as S. typhimurium, have become leading causes of hospital admissions in Sub-Saharan Africa. In collaboration with Dr. Dandekar we have established a rhesus macaque model to study how infection with simian immunodeficiency virus (SIV) causes defects in mucosal barrier function that facilitate systemic dissemination of S. typhimurium. We are using immunological and genomic approaches to map the host response in this model.
Another focus of research in my lab is to understand the mechanisms by which S. typhimurium colonizes and persists in the intestine. The acute inflammatory reaction triggered by S. typhimurium in the intestinal mucosa results in drastic changes in the lumenal environment that enable the pathogen to outgrow the microbiota. Changes in the luminal environment encountered during inflammation include the release of antimicrobials (e.g. defensins, lipocalin-2, calprotectin and others) and changes in the availability of nutrients. We are currently investigating how S. typhimurium can exploit inflammation to outcompete the resident microbiota. Other factors contributing to intestinal colonization are fimbrial adhesins. Whole genome sequencing has revealed the presence of 13 operons containing fimbrial gene sequences and several genes encoding non-fimbrial adhesins in the S. typhimurium genome. We are currently studying the binding specificities of these adhesins using a variety of approaches, including tissue culture, animal models and glycomics.
2008. Winter, S.E., M. Raffatellu, R.P. Wilson, H. Rüssmann and A.J. Bäumler. The Salmonella enterica serotype Typhi regulator TviA reduces IL-8 production in intestinal epithelial cells by repressing flagellin secretion. Cell. Microbiol., 10:247-261.
2008. Chessa, D., C.W. Dorsey, Maria Winter, and A.J. Bäumler. Binding Specificity of Salmonella Plasmid-Encoded Fimbriae Assessed by Glycomics. J. Biol. Chem. 283:8118-8124.
2008. Briggs H.L., N. Pul, R. Seshadri, M.J. Wilson, C. Tersteeg, K.E. Russel-Lodrigue, M. Andoh, A.J. Bäumler and J.E. Samuel. A limited role for iron regulation in Coxiella burnetii pathogenesis. Infect. Immun. 76:2189-2201.
2008. Chessa, D., M. G. Winter, S.-P. Nuccio, Ç. Tükel and A.J. Bäumler. RosE represses Std fimbrial expression in Salmonella enterica serotype Typhimurium. Mol. Microbiol., 68:573-578.
2008. M. Raffatellu, R.L .Santos, D. Verhoeven, M.D. George, R.P. Wilson, S.E. Winter, I. Godinez, S. Sankaran, T.A. Paixao, M.A. Gordon, J.K. Kolls, S. Dandekar, and A.J. Bäumler. Simian immunodeficiency virus–induced mucosal IL–17 deficiency promotes Salmonella dissemination from the gut. Nature Medicine. 14:421-428.
2008. Wilson, R.P., M. Raffatellu, D. Chessa, S.E. Winter, Ç. Tükel, and A.J. Bäumler. The Vi capsule prevents Toll-Like Receptor 4 recognition of Salmonella. Cell. Microbiol., 10:876-890.
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.
2008. Tsolis, R.M. G.M. Young, J.V. Solnick and A.J. Bäumler. From bench to bedside: stealth of enteroinvasive pathogens. Nature Rev. Microbiol. 6:883-892.
2008. Jakomin, M., D. Chessa, A.J. Bäumler, and J. Casadesus. Regulation of the Salmonella enterica std fimbrial operon by DNA adenine methylation, SeqA and HdfR. J. Bacteriol. 190:7406-7413.
2008. Bogomolnaya, L.M., C. Santiviago, H.-J. Yang, A.J. Bäumler and H.L. Andrews-Polymenis. ‘Form Variation’ of the O12 Antigen is Critical for Persistence of Salmonella Typhimurium in the Murine Intestine. Mol. Microbiol. 10:1105-1119.
2009. Godinez, I., M. Raffatellu, T.A. Paixão, T. Haneda, R.L. Santos, R.M. Tsolis and A.J. Bäumler. IL-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. Infect. Immun. 77:387-398.
2009. Chessa, D., M.G. Winter, M. Jakomin, and A.J. Bäumler. Salmonella enterica serotype Typhimurium Std fimbriae bind terminal a(1,2)fucose residues in the cecal mucosa. Mol. Microbiol. 71:864-875.
2009. Figueiredo J.F., S.D. Lawhon, K. Gokulan, S. Khare, M. Raffatellu, R.C. Burghardt, R.M. Tsolis, A.J. Bäumler, B. McCormick, L.G. Adams. Salmonella Typhimurium SipA induces CXC-chemokine expression through p38MAPK and JUN pathways. Microb. Infect. 11:302-310.
2009. Winter, S.E., P. Thiennimitr, S.-P. Nuccio, T. Haneda, M.G. Winter, R.P. Wilson, J.M. Russell, T. Henry, Q.N. Tran, S.D. Lawhon, G. Gomez, C.L. Bevins, H. Ruessmann, D. Monack, L.G. Adams, A.J. Bäumler. Contribution of flagellin pattern recognition to intestinal inflammation during Salmonella enterica serotype Typhimurium infection. Infect. Immun. 77:1904-1916.
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. Bäumler. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe. 5:476-486.
2009. Haneda, T., S.E. Winter, B.P. Butler, R.P. Wilson, Ç. Tükel, M.G. Winter, I. Godinez, R.M. Tsolis and A.J. Bäumler. The capsule-encoding viaB locus reduces intestinal inflammation by a Salmonella Pathogenicity Island 1-independent mechanism. Infect. Immun. 77:2932-2942.
2009. Tükel, Ç., R.P. Wilson, M. Pezeshki, B.A. Chromy and A.J. Bäumler. Responses to amyloids of microbial and host origin are mediated through Toll-like receptor 2. Cell Host Microbe. 6:45-53.
2009. Figueiredo J.F., R. Barhoumi, M. Raffatellu, S.D. Lawhon, L. Rousseau, R.C. Burghardt, R.M. Tsolis, A.J. Bäumler, L.G. Adams. Salmonella enterica serovar Typhimurium-induced internalization and IL-8 expression in HeLa cells does not have a direct relationship with intracellular Ca2+ levels. Microb. Infect. 11:850-858.
2009. Winter, S.E., M.G. Winter, P. Thiennimitr, V.A. Gerriets, S.-P. Nuccio, H. Rüssmann, A.J. Bäumler. The TviA auxiliary protein renders the Salmonella enterica serotype Typhi RcsB regulon responsive to changes in osmolarity. Mol. Microbiol. 74:175-193.
2009. Santos, R.L., M. Raffatellu, C.L. Bevins, L.G. Adams, Ç. Tükel, R.M. Tsolis and A.J. Bäumler. Life in the inflamed intestine, Salmonella style. Trends Microbiol. 17:498-506.
2010. Tran, Q.T., G. Gomez, S. Khare, S.D. Lawhon, M. Raffatellu, A.J. Bäumler, and L.G. Adams. The Salmonella enterica serotype Typhi Vi capsular antigen is expressed after entering the ileal mucosa. Infect. Immun. 78:527-535.
2010. Nunes, J., S.D. Lawhon, C.A. Rossetti, S. Khare, J.F. Figueiredo, T. Gull, R.C. Burghardt, A.J Bäumler, R.M. Tsolis, H.L. Andrews-Polymenis, L.G. Adams. Morphologic and Cytokine Profile Characterization of Salmonella enterica serotype Typhimurium Infection in Calves with Bovine Leukocyte Adhesion Deficiency. Vet. Pathol. 47:322-333.
2010. Raffatellu, M. and A.J. Bäumler. Salmonella’s iron armor for battling the host and its microbiota. Gut Microbes. 1:24-26.
2010. Dandekar, S., M. George and A.J. Bäumler. Th17 cells, HIV and the gut mucosal barrier. Curr. Opin. HIV AIDS. 5:173-178.
2010. Andrews-Polymenis, H.L., A.J. Bäumler, B.A. McCormick and F.C. Fang. Taming the Elephant: Salmonella Biology, Pathogenesis and Prevention. Infect. Immun. 78:2356-2369.
2010. Winter, S.E., A.M. Keestra, R.M. Tsolis and A.J. Bäumler. The blessings and curses of intestinal inflammation. Cell Host & Microbe. In press.
2010. Nuccio, S.-P., N. Thomson, M. Fookes and A.J. Bäumler. Chapter 14, Fimbrial signature arrangements in Salmonella, In. Porwollik, S. (eds.), Salmonella enterica: Genomics and Molecular Biology, Horizon Scientific Press, in Press.
2010. Tükel, Ç., J.H. Nishimori, R.P. Wilson, A.M. Keestra, J.P.M. van Putten and A.J. Bäumler. Toll-like receptors 1 and 2 cooperatively mediate immune responses to curli, a common amyloid from enterobacterial biofilms. Cell. Microbiol. In press.
2010. Winter, S.E., M.G. Winter, I. Godinez, H.-J. Yang, H. Rüssmann, H.L. Andrews-Polymenis, A.J. Bäumler. A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella. PLoS Pathogens. In press.
Former Lab Members
Former Ph.D. students
Tracy L. Nicholson (Currently Microbiologist at USDA, Ames, Iowa)
Stacy M. Townsend (Currently Sen. Research Microbiologist, BioSTAR West, Claremont, CA)
Andrea D. Humphries
R. Paul Wilson (Currently Postdoctoral Fellow at the University of Pennsylvania, Philadelphia, PA)
Former Postdocs and Visiting Professors
Robert A. Kingsley, Ph.D. (Currently Deputy Head, Team 15, Sanger Centre, UK)
Helene Andrews-Polymenis, DVM Ph.D. (Currently Assist. Professor at Texas A&M Univ.)
Manuela Raffatellu, MD (Currently Assist. Professor at the Univ. of California, Irvine)
Caleb Dorsey, Ph.D. (Currently Research Associate, ConjuGon, Madison, WI)
Mustafa Akçelik, Ph.D. (Currently Associate Professor, University of Ankara, Turkey)
Renato de Lima Santos, DVM Ph.D. (Currently Professor Adjunto, UFMG, Brasil)
Daniela Chessa, Ph.D. (Currently Research Associate, Univ. Sassari, Italy)
Takeshi Haneda, Ph.D. (Currently Assist. Professor, Kitasato Univ., Japan)
Çagla Tükel, Ph.D. (Currently Assist. Professor at Temple University, Philadelphia, PA)
Current Lab Members
Maria G Winter (Lab Manager)
Parameth Thiennimitr, MD
Sebastian E. Winter, Ph.D.
Marijke Keestra, Ph.D.
Torsten Sterzenbach, Ph.D.
Robert Crawford, Ph.D.