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Updated: Oct 23, 2025

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
The bacteriophage LUZ24 "Igy" peptide inhibits the Pseudomonas DNA gyrase
Jeroen De Smet1, Jeroen Wagemans1, Maarten Boon1
1Laboratory of Gene Technology, Department of Biosystems, KU Leuven, 3001 Leuven, Belgium.
Abstract:
The bacterial DNA gyrase complex (GyrA/GyrB) plays a crucial role during DNA replication and serves as a target for multiple antibiotics, including the fluoroquinolones. Despite it being a valuable antibiotics target, resistance emergence by pathogens including Pseudomonas aeruginosa are proving problematic. Here, we describe Igy, a peptide inhibitor of gyrase, encoded by Pseudomonas bacteriophage LUZ24 and other members of the Bruynoghevirus genus. Igy (5.6 kDa) inhibits in vitro gyrase activity and interacts with the P. aeruginosa GyrB subunit, possibly by DNA mimicry, as indicated by a de novo model of the peptide and mutagenesis. In vivo, overproduction of Igy blocks DNA replication and leads to cell death also in fluoroquinolone-resistant bacterial isolates. These data highlight the potential of discovering phage-inspired leads for antibiotics development, supported by co-evolution, as Igy may serve as a scaffold for small molecule mimicry to target the DNA gyrase complex, without cross-resistance to existing molecules.
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