Journal Article

The repertoire of resistance mutations selected by a Pseudomonas aeruginosa type IV pilus-targeting lytic bacteriophage

Lahane, Tanisha S., Burrows, Lori L., Tran, Veronica N., Harvey, Hanjeong

2026

Overview

As the use of phages to treat antibiotic-resistant pathogens such as Pseudomonas aeruginosa increases, it is important to understand the potential outcomes of phage exposure. Most therapeutic P. aeruginosa phages use lipopolysaccharides or type IV pili (T4P) as primary receptors. Studying the properties of strains resistant to T4P-targeting phages can guide the design of phage cocktails to mitigate treatment resistance. We show that depending on the mutation, some phage-resistant strains can revert to wild-type sequences, emphasizing the importance of combining diverse phages to suppress resurgence. By characterizing mutations that confer resistance, we can better understand whether pilus structural or regulatory components are more likely to be lost. Using phages to select for the loss of pilus function represents an unbiased approach to identify new mutations in pilus-related proteins, shedding light on understudied components. Building a database of such mutations will help guide strategies to target and disarm this key P. aeruginosa virulence factor.

• Publisher: American Society for Microbiology
• Subject: Bacterial Pili / Bacteriophage Genetics / Bacteriophage-Pathogen Interactions / Clinical Microbiology and Infectious Diseases / Microbial Genetics / Microbial Pathogenesis and Immunology / Microbial Physiology and Genetics / Model Bacteriophages (E.g., Lambda, T5, P22, 933w, P4) / Pathogen Biology and Host Interaction / Phage Entry and Penetration / Phage Resistance Mechanisms / Phage-Host Interactions / Pili and Fimbriae / Pili Mutants / Pilin Genes / Research Article / Surface Adhesion Mechanisms / Surface Structures