Occurrence and functionality of antimicrobial peptides in the gastrointestinal tract
The interaction of the luminal bacterial flora with the intestinal mucosa plays an important role in the pathophysiology of inflammatory bowel diseases as ulcerative colitis and Crohn’s disease. As part of the innate defense the intestinal mucosa synthesizes broad-spectrum antimicrobial peptides as lysozyme, cathelicidins and defensins to avoid overgrowth of luminal bacteria, mucosal attachment and the invasion of potential pathogens.
Data based on RT-PCR and immunohistochemistry indicate that the pattern of defensin-expression in the gastrointestinal epithelium is deficient in Crohn’s disease. We could show that this leads to a diminished mucosal killing of luminal and pathogenic bacteria. It is therefore possible that the alteration of mucosal antimicrobial peptides plays an important role in the development of inflammatory bowel disease. In ulcerative colitis variations of synthesis and chemical composition of the mucus may lead to a decreased retention of antimicrobial peptides.
The focus of our research is the purification of antimicrobial peptides from mucus and mucosa and how this peptide pattern may relate to the pathogenesis of ulcerative colitis and Crohn’s disease.
In addition, we investigate the antibacterial and antifungal spectra of the isolated peptides against the luminal flora and pathogens.
Data based on RT-PCR and immunohistochemistry indicate that the pattern of defensin-expression in the gastrointestinal epithelium is deficient in Crohn’s disease. We could show that this leads to a diminished mucosal killing of luminal and pathogenic bacteria. It is therefore possible that the alteration of mucosal antimicrobial peptides plays an important role in the development of inflammatory bowel disease. In ulcerative colitis variations of synthesis and chemical composition of the mucus may lead to a decreased retention of antimicrobial peptides.
The focus of our research is the purification of antimicrobial peptides from mucus and mucosa and how this peptide pattern may relate to the pathogenesis of ulcerative colitis and Crohn’s disease.
In addition, we investigate the antibacterial and antifungal spectra of the isolated peptides against the luminal flora and pathogens.
Major Projects
- Purification of antimicrobial peptides from mucus and mucosa of healthy controls
- Pattern of antimicrobial peptides in inflammatory bowel disease
- Antimicrobial spectra of isolated peptides against aerobic/anaerobic bacteria and fungi
Dr. Sabine Nuding
phone: ++49-711-8101 3736
Selected References
- Nuding S, Zabel LT, Enders C, Porter E, Fellermann K, Wehkamp J, Mueller HA, Stange EF: Antibacterial activity of human defensins on anaerobic intestinal bacterial species: a major role of HBD-3. Microbes Infect 2009; 11(3):384-93.
- Möndel M, Schroeder BO, Zimmermann K, Huber H, Nuding S, Beisner J, Fellermann K, Stange EF, Wehkamp J: Probiotic E. coli treatment mediates antimicrobial human ß-defensin synthesis and fecal excretion in humans. Mucosal Immunol 2009; 2(2):166-72.
- Hosaka Y, Koslowski M, Nuding S, Wang G, Schlee M, Schäfer C, Saigenji K, Stange EF, Wehkamp J: Antimicrobial host defense in the upper gastrointestinal tract. Eur J Gastroenterol Hepatol 2008; 20(12):1151-8.
- Nuding S, Fellermann K, Wehkamp J, Stange EF. Reduced mucosal antimicrobial activity in Crohn's disease of the colon. Gut 2007; 56(9):1240-7.
- Nuding S, Fellermann K, Wehkamp J, Mueller HA, Stange EF. A flow cytometric assay to monitor antimicrobial activity of defensins and cationic tissue extracts. J Microbiol Methods 2006; 65(2):335-45.
- Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H Jr, Fellermann K, Ganz T, Stange EF, Bevins CL. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A. 2005; 102(50):18129-34.
- Wehkamp J, Harder J, Wehkamp K, Wehkamp-von Meissner B, Schlee M, Enders C, Sonnenborn U, Nuding S, Bengmark S, Fellermann K, Schröder JM, Stange EF. NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun. 2004; 72(10):5750-8.
Major Networks and Collaborations
- Edith Porter, Department of Biological Sciences, California State University, Los Angeles
- Lutz T. Zabel, Institute of Laboratory Medicine, Kliniken des Landkreises Göppingen
Curriculum Vitae Sabine Nuding, PhD
Affiliation
Graduate biologist
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart Germany
phone ++49-(0)711-8101 3736
fax ++49 (0)711-85 92 95
email sabine.nuding@ikp-stuttgart.de
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart Germany
phone ++49-(0)711-8101 3736
fax ++49 (0)711-85 92 95
email sabine.nuding@ikp-stuttgart.de
Education and Professional Career
| 1991-1998 | Study of biology, University of Hohenheim |
| 1998 | Diploma |
| 1998-2002 | PhD student, University of Hohenheim |
| 2003 | Doctor’s degree |
| 2003-present | Postdoc, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology |