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Precision Antimicrobial Therapy Against Fusobacterium nucleatum Using Bioengineered Probiotics Expressing Guided

Ankan Choudhury1,2, Colin Scano1, Allison Barton1

  • 1Department of Biology, College of Arts & Sciences, Baylor University, Waco, Texas, USA.

Microbial Biotechnology
|December 10, 2025
PubMed
Summary

A novel bioengineered probiotic selectively targets Fusobacterium nucleatum (F. nucleatum), a key driver of colorectal cancer (CRC). This approach shows promise for a targeted CRC therapy with minimal impact on gut microbiota diversity.

Keywords:
Fusobacteriumantimicrobial peptidesbioengineeringcolon cancerprobiotics

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Bioengineering

Background:

  • Colorectal cancer (CRC) is a major cause of cancer mortality.
  • Fusobacterium nucleatum (F. nucleatum) significantly contributes to CRC progression.
  • Targeting F. nucleatum presents a therapeutic opportunity for CRC.

Purpose of the Study:

  • To develop and evaluate a bioengineered probiotic expressing guided antimicrobial peptides (gAMPs) for selective F. nucleatum inhibition.
  • To assess the efficacy of gAMPs in targeting F. nucleatum in vitro and in a simulated gut microbiome.
  • To determine the impact of gAMP treatment on microbial diversity and gut microbiota composition.

Main Methods:

  • Engineered Lactococcus lactis MG1363 to express Ovispirin and SCF-derived gAMPs guided by a Statherin peptide.
  • Assayed antimicrobial activity, biofilm inhibition, and growth kinetics of gAMPs and the probiotic.
  • Conducted co-culture experiments in a simulated human gut microbiome using quantitative PCR and 16S rRNA sequencing.

Main Results:

  • Statherin-derived guide peptide enhanced binding affinity to F. nucleatum.
  • Both unguided and guided antimicrobial peptides (AMPs) inhibited F. nucleatum biofilm formation.
  • gAMPs demonstrated selective toxicity towards F. nucleatum, reduced toxicity to non-target bacteria, and preserved gut microbial diversity in co-culture.
  • gAMP probiotic treatment effectively reduced F. nucleatum abundance while maintaining microbiota richness.

Conclusions:

  • Bioengineered probiotics expressing gAMPs offer a promising targeted therapeutic strategy against F. nucleatum in CRC.
  • This approach selectively targets pathogenic bacteria while preserving beneficial gut microbiota.
  • Further development could lead to novel treatments for CRC and other F. nucleatum-associated diseases.