University of California, Davis One Shields Avenue Rm 5513 Genome and Biomedical Sciences Building Davis California 95616 Tel: (530) 530-754-7225 Lab: (530) 754-8534 FAX: (530) 754-7240 ajbaumler@ucdavis.edu

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

 Member of the Graduate Group of Microbiology

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, which is caused by non-typhoidal Salmonella serotypes (e.g. S. typhimurium), is a typical diarrheal disease characterized by a massive neutrophil influx in the terminal ileum and colon. In contrast, typhoid fever, which is caused by Salmonella typhi, is not a diarrheal disease and intestinal infiltrates are dominated by mononuclear cells (i.e. macrophages and dendritic cells). We have found that the neutrophil influx during gastroenteritis is caused by bacterial invasion (mediated by the invasion associated type III secretion system, T3SS-1), followed by innate immune recognition of S. typhimurium (through Toll-like receptors) and survival in mononuclear cells (mediated by a second type III secretion system, T3SS-2). S. typhi is able to prevent neutrophil infiltration by expressing a virulence factor, the Vi-capsular antigen, that reduces Toll-like receptor signaling in the intestinal mucosa. We are further studying the molecular mechanisms underlying the pathogenesis of gastroenteritis and typhoid fever using a variety of in vivo, ex vivo and tissue culture models.

A second focus of research in my lab is to understand the role of adhesins during S. typhimurium intestinal colonization and persistence. Intestinal persistence of Salmonella serotypes in apparently healthy livestock and domestic fowl leads to their subsequent introduction into the derived food products, thereby resulting in animal to human transmission. Although this route of infection is largely responsible for the estimated 1.4 million annual cases of Salmonella-induced enterocolitis in the U.S. , the molecular mechanisms responsible for intestinal persistence in healthy food animals are unknown. 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.

1999. Tsolis, R.M., L. G. Adams, T. A. Ficht, and A. J. Bäumler. Contribution of Salmonella typhimurium virulence factors to diarrheal disease in calves. Infect. Immun. 67:4879-4885.

1999. Norris, T.L., and A.J. Bäumler. Phase variation of the lpf fimbrial operon is a mechanism to evade cross immunity between Salmonella serotypes. Proc. Natl. Acad. Sci. USA. 96:13393-13398.

1999. Vazquez-Torres, A., J. Jones-Carson, A.J. Bäumler, S. Falkow , W. Brown, M. Le, R. Breggen, T. Parks, and F.C. Fang. Extraintestinal dissemination of Salmonella via CD18-expressing phagocytes. Nature. 401:804-808.

2000. Bäumler, A.J., B.M. Hargis, and R.M. Tsolis. Tracing the origins of Salmonella outbreaks. Science. 287:50-52.

2002. Kingsley, R.A., R.L. Santos, A.M. Keestra, L.G. Adams and A.J. Bäumler. Salmonella enterica serovar Typhimurium ShdA is an outer membrane fibronectin binding protein that is expressed in the intestine. Mol. Microbiol. 43:897-908.

2002. Zhang, S., R.L. Santos, R.M. Tsolis, S. Stender, W.D. Hardt, A.J. Bäumler, and L.G. Adams. SipA, SopA, SopB, SopD and SopE2 act in concert to induce diarrhea in calves infected with Salmonella enterica serotype Typhimurium. Infect. Immun. 70:3843-3855.

2003. Humphries, A.D., M. Raffatellu, S. Winter, E.H. Weening, R.A. Kingsley, R. Droleskey, S. Zhang, J. Figueiredo, S. Khare, J. Nunes, L.G. Adams, R.M. Tsolis and A.J. Bäumler. The use of flow cytometry to detect expression of subunits encoded by eleven Salmonella enterica serotype Typhimurium fimbrial operons. Mol. Microbiol. 48:1357-1376.

2004. Kingsley, R.A., A. M. Keestra, M. R. de Zoete and A. J. Bäumler. The ShdA adhesin binds to the cationic cradle of the fibronectin 13 FnIII repeat module: evidence for molecular mimicry of heparin binding. Mol. Microbiol. 52:345-355.

2005. Raffatellu, M., R. P. Wilson, D. Chessa, H. Andrews-Polymenis, Q. T. Tran, S. Lawhon, S. Khare, L. G. Adams and A. J. Bäumler. SipA, SopA, SopB, SopD and SopE2 contribute to Salmonella enterica serotype Typhimurium invasion of epithelial cells. Infect. Immun. 73:146-154.

2005. Weening, E.H., J.D. Barker, M.C. Laarakker, A.D. Humphries, R.M. Tsolis and A.J. Bäumler. The Salmonella enterica serotype Typhimurium lpf , bcf , stb , stc , std , and sth fimbrial operons are required for intestinal persistence in mice . Infect. Immun. 73:3358-3366.

2005. Dorsey, C.W., M.C. Laarakker, A.D. Humphries and A.J. Bäumler. Salmonella enterica serotype Typhimurium MisL is an intestinal colonization factor that binds fibronectin. Mol. Microbiol. 57:196-211.

2005. Raffatellu, M., D. Chessa, R.P. Wilson, R. Dusold, S. Rubino and A.J. Bäumler. The Vi-capsular antigen of Salmonella enterica serotype Typhi reduces Toll-like receptor-dependent IL-8 expression in the intestinal mucosa. Infect. Immun. 73:3367-3374.