Poster Presentation International Peptide Symposium 2023

Development of venom-derived peptides as gut-specific therapeutics to target mucosal biofilms in patients with gastrointestinal disorders   (#266)

Bernhard Jandl 1 2 3 4 , Michaela Lang 4 , Athanasios Makristathis 5 , Christoph Gasche 4 6 , Markus Muttenthaler 1 3
  1. Faculty of Chemistry, Institute of Biological Chemistry, University of Vienna, Vienna, Austria
  2. University of Vienna, Vienna Doctoral School in Chemistry (DoSChem), Vienna, Austria
  3. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
  4. Department of Internal Medicine 3, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
  5. Department of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria
  6. Loha for Life, Center for Gastroenterology and Iron Deficiency, Vienna, Austria

 Gastrointestinal disorders, such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD, including Crohn’s disease and ulcerative colitis), affect 10–15% of the global population resulting in a substantial socioeconomic burden on our society.[1] Mucosal biofilms are mucus-adherent prokaryotic communities embedded in a protective layer of extracellular substances displaying high antibiotic resistance[2] and occur in 57% of IBS patients and 34% of ulcerative colitis patients.[3] Animal venom is a rich source of bioactive peptides that have been fine-tuned throughout evolution for diverse physiological activities. Numerous venom-derived peptides display potent antimicrobial activity, representing valuable therapeutic opportunities for treating infectious diseases.[4] However, the full potential of such peptides against gut mucosal biofilms has not been revealed yet. Our approach focuses on developing gut biofilm-targeting peptides, including (i) synthesis of venom-derived peptides from diverse animal species, (ii) screening for biofilm-specific activity against bacterial isolates from biofilm-positive patients, and (iii) chemical strategies to improve our leads’ gut stability and therapeutic window. Here, we report our latest results in developing venom-derived antibiofilm peptide therapeutics for treating mucosal biofilms in patients with gastrointestinal disorders.

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  2. H.-C. Flemming, J. Wingender, U. Szewzyk, P. Steinberg, S. A. Rice, S. Kjelleberg, Nature Reviews Microbiology 2016, 14, 563-575.
  3. M. Baumgartner, M. Lang, H. Holley, D. Crepaz, B. Hausmann, P. Pjevac, D. Moser, F. Haller, F. Hof, A. Beer, E. Orgler, A. Frick, V. Khare, R. Evstatiev, S. Strohmaier, C. Primas, W. Dolak, T. Köcher, K. Klavins, T. Rath, M. F. Neurath, D. Berry, A. Makristathis, M. Muttenthaler, C. Gasche, Gastroenterology 2021, 161, 1245-1256.e1220.
  4. aR. Spohn, L. Daruka, V. Lázár, A. Martins, F. Vidovics, G. Grézal, O. Méhi, B. Kintses, M. Számel, P. K. Jangir, B. Csörgő, Á. Györkei, Z. Bódi, A. Faragó, L. Bodai, I. Földesi, D. Kata, G. Maróti, B. Pap, R. Wirth, B. Papp, C. Pál, Nat. Commun. 2019, 10, 4538; bJ. Koehbach, D. J. Craik, Trends Pharmacol. Sci. 2019, 40, 517-528; cD. Pletzer, R. E. W. Hancock, J. Bacteriol. 2016, 198, 2572-2578.