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Department of Medical Microbiology and Immunology

Department of Medical Microbiology and Immunology

Andreas Baumler, Ph.D.

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

Recent/Current
Research Funding

 

 

Graduate Group Affiliations

Microbiology

Immunology

Comparative Pathology

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 tight regulation of virulence gene expression during the transition from the intestinal lumen into the intestinal mucosa enables this pathogen to evade detection by the innate immune system, thereby penetrating defenses that prevent bacterial dissemination. This example illustrates how the outcome of host pathogen interaction at the intestinal mucosal interface can alter the clinical presentation and dictate the disease outcome.

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)- 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 harness benefit from the host response to 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

 

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)

 

Recent/Current Teaching

 

 

Teaching and Research Awards