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Analysis of engineered T7 bacteriophages containing genetic sequences encoding antimicrobial peptides
Tobias Ludwig1, Daniela Volke1, Andor Krizsan1
1Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Center for Biotechnology and Biomedicine, Leipzig University, Leipzig, Germany.
Frontiers in Antibiotics
|January 30, 2025
Summary
Researchers engineered bacteriophages to produce antimicrobial peptides, enhancing their ability to combat multi-drug resistant bacteria like E. coli. This novel phage therapy approach shows promise against resistant bacterial strains.
Area of Science:
- Microbiology
- Biotechnology
- Antimicrobial Resistance
Background:
- The rise of multi- and pan-resistant bacteria necessitates novel therapeutic strategies.
- Bacteriophage therapy offers a promising alternative to conventional antibiotics.
- Previous work demonstrated genetically modified T7 bacteriophages producing antimicrobial peptides (AMPs).
Purpose of the Study:
- To optimize the expression of apidaecin derivatives within T7 bacteriophages.
- To enhance the efficacy of phage-based antimicrobial strategies against resistant *Escherichia coli*.
- To investigate the synergistic effects of combining bacteriophages with AMPs.
Main Methods:
- Genetic modification of T7 bacteriophages to express apidaecin derivatives (Api805) with OmpA secretion signal.
- Construction of phages with single and double copies of the *OmpA*-Api805 insert.
- Engineering phages to express DNA sequences from cathelicidin-related AMP (CRAMP) and melittin.
- Evaluating the antimicrobial activity of engineered phages against phage-resistant *E. coli*.
Main Results:
- T7 phages with two copies of the *OmpA*-Api805 insert showed improved inhibition of phage-resistant *E. coli*.
- The OmpA secretion signal peptide prevented detrimental effects of the peptide on the host cell.
- Combinatorial use of T7 phages with CRAMP and melittin enhanced bacterial lysis and prevented resistance development.
- Engineered T7Select-(M)CRAMP and T7Select-(M)melittin phages partially inhibited resistant *E. coli* growth post-lysis.
Conclusions:
- Genetically engineered bacteriophages expressing antimicrobial peptides represent a viable strategy against resistant bacteria.
- Optimizing peptide expression and secretion enhances phage efficacy.
- Combining bacteriophage therapy with antimicrobial peptides can overcome bacterial resistance mechanisms.
- This approach holds potential for developing new treatments for bacterial infections.
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