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Department of Medical Microbiology and Immunology

Department of Medical Microbiology and Immunology

Andreas Bäumler, Ph.D.

Professor
Vice Chair of Research
GBSF Room 5513
Davis Campus
(530) 754-7225
e-mail 

Graduate Group Affiliations

Microbiology

Immunology

Comparative Pathology


Education

Ebehard-Karls Universität, Tübingen, Germany, Diplom (B.S.) Microbiology
Ebehard-Karls Universität, Tübingen, Germany, Dr. rer. nat. (Ph.D.) Microbiology
Oregon Health Sciences University, Portland, Oregon, Post-Doc Microbiology

Research Interests

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 caused most frequently by Salmonella serotypes worldwide are typhoid fever and gastroenteritis. 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 caused by non-typhoidal Salmonella serotypes (e.g. S. typhimurium) is a localized infection with short incubation period (<24 hours on average). In contrast, typhoid fever caused by the human-adapted S. typhi is a severe systemic infection with a two-week incubation period. The host restricts dissemination of S. typhimurium by mounting acute inflammatory responses characterized by the recruitment of neutrophils. However, S. typhi can bypass these defenses and cause an invasive bloodstream infection. Our work on virulence mechanisms of S. typhi suggests that expression of a capsular polysaccharide and altered virulence gene expression act in concert to evade detection by the innate immune system, thereby enabling the pathogen to penetrate defenses that prevent bacterial dissemination. Thus, the presence of certain virulence traits, such as a capsule or altered virulence gene regulation, can drastically attenuate host responses in the intestinal mucosa and alter the clinical presentation associated with otherwise closely related bacterial pathogens.

A second focus in the lab is to understand the mechanisms by which the innate immune system detects microbial invasion and how the consequent inflammatory response alters growth conditions in the intestinal lumen. We study how the innate immune system detects mucosal invasion by S. Typhimurium through Toll-like receptors, NOD-like receptors and complement. We are also interested in how initial responses generated by bacterial host cell interaction are amplified in tissue through the interleukin (IL)-18/interferon (IFN)-γ and the IL-23/IL-17 axes, which results in the activation of mucosal barrier functions against S. typhimurium dissemination. Finally, we are investigating how the pathogen can survive antimicrobial defenses encountered in the lumen of the inflamed intestine. The intestine is host to a diverse bacterial community whose structure, at the phylum level, is maintained through unknown mechanisms. Acute inflammation triggered by S. typhimurium is accompanied by changes in the bacterial community structure marked by an outgrowth of the pathogen. Our studies show how S. typhimurium can use specific metabolic traits to harness benefit from the host response and edge out the beneficial bacterial species that dominate in the healthy gut. The elucidation of how S. Typhimurium alters the bacterial community structure during gastroenteritis is beginning to provide insights into mechanisms that dictate the balance between the host and its microbiota. 

Representative Publications 

A full list of my published work can be found at: http://www.ncbi.nlm.nih.gov/pubmed/?term=baumler+aj

2014. Lopez, C.A., D.D. Kingsbury, E.M. Velazquez and A.J. Bäumler. Collateral Damage: Microbiota-derived Metabolites and Immune Function in the Antibiotic Era. Cell Host & Microbe. 16(2):156-163.

2014. Hirao, L.A, I. Grishina, O. Bourry, W.K. Hu, M. Somrit, S. Sankaran-Walters, C.A. Gaulke, A.N. Fenton, J.A. Li, R.W. Crawford, F. Chuang, R. Tarara, M. Marco, A.J. Bäumler, H. Cheng and S. Dandekar. Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1b Production and Initiates Gut Epithelial Disruption. PLOS Pathogens. 10: e1004311.

2014. Winter, S.E., M.G. Winter, V. Poon, A.M. Keestra, T. Sterzenbach, F. Faber, and A.J. Bäumler. Salmonella enterica serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation. PLOS Pathogens. 10: e1004207.

2014. Wangdi, T, C.-Y. Lee, A.M. Spees, C. Yu, D.D. Kingsbury, S.E. Winter, C.J. Hastey, R.P. Wilson, V. Heinrich* and A.J. Bäumler*. The Vi capsular polysaccharide enables Salmonella enterica serovar Typhi to evade microbe-guided neutrophil chemotaxis. PLOS Pathogens. 10: e1004306.

2014. Lokken, K.L., R.M. Tsolis and A.J. Bäumler. Hypoferremia of infection: a double-edged sword? Nature Medicine. 20:335-337.

2014. O’Donnell, H., O. Pham, L.-X. Li, S.-P. Nuccio, D. Monack, A.J. Bäumler, and S.J. McSorley. Innate bactericidal capacity of Th1 cells is tuned by TLR and inflammasome signaling. Immunity. 40: 213–224.

2014. Hirao, L.A, I. Grishina, O. Bourry, W.K. Hu, M. Somrit, S. Sankaran-Walters, C.A. Gaulke, A.N. Fenton, J.A. Li, R.W. Crawford, F. Chuang, R. Tarara, M. Marco, A.J. Bäumler, H. Cheng and S. Dandekar. Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1b Production and Initiates Gut Epithelial Disruption. PLOS Pathogens. 10: e1004311.

2014. Nuccio, S.-P. and A.J. Bäumler. Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut. mBIO. 5: e00929-14.

2014. Laughlin, R.C., L.A. Knodler, R. Barhoumi, H.R. Payne, J. Wu, G. Gomez, R. Pugh, S.D. Lawhon, A.J. Bäumler, O. Steele-Mortimer, L.G. Adams. Spatial segregation of virulence gene expression during acute enteric infection with Salmonella enterica serovar Typhimurium. mBIO. 5: e00946-13.

2013. Keestra, A.M., M.G. Winter, J.J. Auburger, S.P. Fräßle, M.N. Xavier, S.E. Winter, A. Kim, V. Poon, M.M. Ravesloot, J. Waldenmaier, R.M. Tsolis, R.A. Eigenheer and A.J. Bäumler. Manipulation of small Rho GTPases is a pathogen-induced process detected by Nod1. Nature. 496:233-237.

2013. Sterzenbach, T., K.T. Nguyen, S.-P. Nuccio, M.G. Winter, C. Vakulskas, S. Clegg, T. Romeo and A.J. Bäumler. A novel CsrA titration mechanism regulates fimbrial gene expression in Salmonella Typhimurium. EMBO J. 32:2872-2883.

2013. Xavier, M.N., M.G. Winter, A.M. Spees, K. Nguyen, V.L. Atluri, T.A.M. Silva, A.J. Bäumler, W. Müller3, R.L. Santos2, R.M.Tsolis. CD4+ T cell derived IL-10 promotes Brucella abortus persistence through modulation of macrophage function during early infection. PLOS Pathogens. 9: e1003454.

2013. Crawford, R.W., T. Wangdi, A.M. Spees, M.N. Xavier, R.M. Tsolis and A.J. Bäumler. Loss of very-long O-antigen chains optimizes capsule-mediated immune evasion by Salmonella enterica serovar Typhi. mBIO. 4: e00232-13.

2013. Spees, A.M., C.A. Lopez, D.D. Kingsbury, S.E. Winter and A.J. Bäumler. Colonization resistance: battle of the bugs or ménage à trois with the host? PLOS Pathogens. 9: e1003730

2013. Xavier, M.N., M.G. Winter, A.M. Spees, K. Nguyen, V.L. Atluri, A.B. den Hartigh, T.M. A. Silva, P.A. Luciw, D.M. Monack, A.J. Bäumler, R.L. Santos, R.M. Tsolis. A PPAR-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages. Cell Host & Microbe. 14:159-170.

2013. Spees, A.M., T. Wangdi, C.A. Lopez, D.D. Kingsbury, M.N. Xavier, S.E. Winter, R.M. Tsolis and A.J. Bäumler. Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration. mBIO. 4: e00430-13.

2013. Rivera-Chávez, F., S.E. Winter, C.A. Lopez, M.N. Xavier, M.G. Winter, J.M. Russell, R.C. Laughlin, S.D. Lawhon, T. Sterzenbach, C.L. Bevins, R.M. Tsolis, R. Harshey, L.G. Adams and A.J. Bäumler. Salmonella uses energy taxis to benefit from intestinal inflammation. PLOS Pathogens. 9(4): e1003267

2013. Winter, S.E., M.G. Winter, M.N. Xavier, P. Thiennimitr, V. Poon, A.M. Keestra, R. Laughlin, G. Gomez, J. Wu, S.D. Lawhon, I. Popova, S.J. Parikh, L.G. Adams, R.M. Tsolis, V.J. Stewart and A.J. Bäumler. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science. In press.

2012. Fang, F.C. and A.J. Bäumler. A Toll gate for typhoid. Cell. 151:473-475.

2012. Crawford, R.W., A.M. Keestra, S.E. Winter, M.N. Xavier, R.M. Tsolis, V. Tolstikov and A.J. Bäumler. Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance. PLoS Pathogens.  8: e1002918. (PMID: 23028318)

2012. Chu, H., M. Pazgier, G. Jung, S.-P. Nuccio, P.A. Castillo, M.F. de Jong, M.G. Winter, S.E. Winter, J. Wehkamp, B. Shen, N.H. Salzman, M.A. Underwood, R.M. Tsolis, G.M. Young, W. Lu, R.I. Lehrer, A.J. Bäumler, and C.L. Bevins. Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science. 337:477-481. (PMID: 22722251)

2012. Lopez, C.A., S.E. Winter, F. Rivera-Chávez, M.N. Xavier, V. Poon, S.-P. Nuccio, R.M. Tsolis and A.J. Bäumler. Phage-mediated acquisition of a type III secreted effector protein boosts growth of Salmonella by nitrate respiration. mBIO. 3:e00143-12. (PMID: 22691391)

2012. Lee, S.-J., J.B McLachlan, J.R. Kurtz, D. Fan, S.E. Winter, A.J. Bäumler, M.K. Jenkins, and S.J. McSorley. Temporal expression of bacterial proteins instructs host CD4 T cell expansion and Th17 development. PLoS Pathogens. 8(1):e1002499. (PMID: 22275869)

2011. Keestra, A.M. and A.J. Bäumler. Host defenses trigger Salmonella’s arsenal. Cell Host & Microbe. 9:167-168. (PMID: 21402352)

2011. Keestra, A.M., M.G. Winter, D. Klein-Douwel, M.N. Xavier, S.E. Winter, A. Kim, R.M. Tsolis and A.J. Bäumler. A Salmonella virulence factor activates the Nod1/Nod2 Signaling Pathway. mBIO. 2:e00266-11. (PMID: 22186610)

2011. Thiennimitr, P., S.E. Winter, M.G. Winter, M.N. Xavier, V. Tolstikov, D.L. Huseby, T. Sterzenbach, R.M. Tsolis, J.R. Roth, A.J. Bäumler. Intestinal inflammation allows Salmonella to utilize ethanolamine to compete with the microbiota. Proc. Natl. Acad. Sci. USA. 108:17480-17485. (PMID: 21969563)

2011. Fookes, M., G.N. Schroeder, G. Langridge, C.J. Blondel, C. Mammina, G.S. Vernikos, K.S. Robinson, N.K. Petty, R.A. Kingsley, A.J. Bäumler, S.-P. Nuccio, I. Contreras, C.A. Santiviago, D. Maskell, P. Barrow, T. Humphrey, A. Nastasi, M. Roberts, G. Frankel, J. Parkhill, G. Dougan, N.R. Thomson. Salmonella bongori provides insights into the evolution of the salmonellae. PLoS Pathogens. 7: e1002191. (PMID: 21876672)

2010. Winter, S.E., A.M. Keestra, R.M. Tsolis and A.J. Bäumler. The blessings and curses of intestinal inflammation. Cell Host & Microbe. 8:36-43. (PMID: 20638640)

2010. Winter S.E., P. Thiennimitr, M.G. Winter, B. Butler, D.L. Huseby, R.W. Crawford, J.M. Russell, C.L. Bevins, L.G. Adams, R.M. Tsolis, J.R. Roth and A.J. Bäumler. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature. 467:426-429. (PMID: 20864996)

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. 6: e1001060. (PMID: 20808848)

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. (PMID: 19454351)

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 (PMID: 19616765)

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. (PMID: 18955984)

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. (PMID: 18376406) 

Former Lab Members 

Former Ph.D. students

Tracy L. Nicholson (Currently Microbiologist at USDA, Ames, Iowa)
http://www.ars.usda.gov/pandp/people/people.htm?personid=44830

Stacy M. Townsend (Currently Sen. Research Microbiologist, BioSTAR West, Claremont, CA)
http://www.synedgen.com/about/team/

Andrea D. Humphries

R. Paul Wilson (Currently postdoc at the University of Pennsylvania, Philadelphia, PA)

Ivan Godinez (Illumina)

Alanna Spees

Parameth Thiennimitr, MD (Currently postdoc at Stanford University)

Sean-Paul Nuccio (Currently postdoc at UC Irvine)

Former Postdocs and Visiting Professors

Robert A. Kingsley, Ph.D. (Research Leader, Institute of food research, UK)
http://www.ifr.ac.uk/research/scientists/rob-kingsley/

Helene Andrews-Polymenis, DVM Ph.D. (Currently Associate. Professor at Texas A&M Univ.)
http://medicine.tamhsc.edu/basic-sciences/mmp/faculty/helene-andrews.html

Manuela Raffatellu, MD (Currently Associate Professor at the Univ. of California, Irvine)
http://www.faculty.uci.edu/profile.cfm?faculty_id=5823

Caleb Dorsey, Ph.D. (Currently Research Associate, ConjuGon, Madison, WI)

Mustafa Akçelik, Ph.D. (Currently Associate Professor, University of Ankara, Turkey)
http://www.science.ankara.edu.tr/eng/index.php?link=3021

Renato de Lima Santos, DVM Ph.D. (Currently Professor, UFMG, Brasil)
http://www.gf.org/fellows/16675-renato-de-lima-santos

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)
http://www.temple.edu/medicine/faculty/t/tukel.asp?pms=%28tukel%20C[au]%29

Robert Crawford, Ph.D. (Currently Assistant Professor at California State University, Sacramento)
http://www.csus.edu/bios/faculty-staff/full-time.html

Torsten Sterzenbach, Ph.D. (Currently Group Leader at the Universität Osnarbrück, Germany)
http://www.dasoertliche.de/Themen/Torsten-Sterzenbach/LinkedIn/torstensterzenbach

Sebastian E. Winter, Ph.D. (Currently Assist. Professor at the University of Texas Southwestern Medical Center, Dallas, TX)
http://www.utsouthwestern.edu/labs/winter-sebastian/about/

Current Lab Members 

Technicians

Briana Young (Lab Manager)
Alfredo Chavez

PhDStudents

Fabian Rivera
Christopher Lopez
Dawn Kingsbury, DVM
Eric Velazquez

Postdocs

Franziska Faber, PhD
Hirotaka Hiyoshi, PhD
Mariana Xavier, PhD
Yael Litvak, PhD

Assistant Project Scientists

Marijke Keestra, PhD
Tamding Wangdi, PhD