Poster Presentation The 16th Australian Peptide Conference 2025

Targeting gastrointestinal biofilms with nature-derived antimicrobial peptides (#223)

Michael Michael 1 , Mark Blaskovich 1 , Markus Muttenthaler 1 2
  1. Centre for Chemistry and Drug Discovery, Institute for Molecular Bioscience, The University of Queensland,, Brisbane, QLD, Australia
  2. Institute of Biological Chemistry, University of Vienna, Vienna, Austria

Gastrointestinal (GI) disorders, such as inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), affect ~6.8 million and ~780 million individuals globally, respectively.1–5 Mucosal-associated biofilms are highly prevalent in the GI tracts of those patients.6 Preliminary clinical work in removing these biofilms with endoscopic flushing reduces functional GI symptoms. Currently, no pharmaceutical interventions exist targeting such gut biofilms. Hence, we explored antibiofilm and antimicrobial peptides (AMPs) from diverse animal clades, including marsupials, monotremes, placental mammals, amphibians, and insects, for the development of oral peptide-based anti-gut-biofilm therapy.

We synthesised the AMPs via solid-phase peptide synthesis and screened against four biofilm-positive patient isolates of Streptococcus parasanguinis 102-K3/3, Streptococcus salivarius 102-K5/2, Bacteroides fragilis 93-K12 and Escherichia coli 104-K1 and two literature-control strains of Staphylococcus aureus ATCC29213 and Pseudomonas aeruginosa ATCC27853 by determining a minimum inhibitory concentration, and assessed antibiofilm activities using crystal violet staining and the Calgary device. We have also conducted structure-stability-activity relationship studies to enhance gut stability and potency of identified peptide leads for oral administration. Here, we showcase our latest results in developing oral anti-gut-biofilm peptide leads for the treatment of gastrointestinal disorders.

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