10 min Rapid Fire International Peptide Symposium 2023

Development of gut-specific antibiofilm peptides to target mucosal biofilms in patients with gastrointestinal disorders (#33)

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 Chron’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 Antimicrobial peptides (AMPs) of natural origin evolved for their activity to combat bacteria,4 representing therapeutic opportunities for treating infectious diseases. However, the full potential of such AMPs against gut mucosal biofilms has not been revealed yet. Our approach focuses on developing gut biofilm-targeting peptides, including (i) synthesis of AMPs from diverse natural sources, (ii) screening for biofilm-specific activity against bacterial isolates from biofilm-positive patients, and (iii) chemical strategies to improve our AMP leads’ gut stability and therapeutic window. Here, we report our latest results in developing gut-specific antibiofilm peptides to treat mucosal biofilms in patients with gastrointestinal disorders.

  1. aG. G. Kaplan, Nat Rev Gastroenterol Hepatol 2015, 12, 720-727; bC. Canavan, J. West, T. Card, Aliment. Pharmacol. Ther. 2014, 40, 1023-1034.
  2. H.-C. Flemming, J. Wingender, U. Szewzyk, P. Steinberg, S. A. Rice, S. Kjelleberg, Nat. Rev. Microbiol. 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.