Isolation of a Novel Lytic Pseudomonas aeruginosa Phage Henu5 and Fitness Costs of Phage-Driven Resistance
Abstract
Phage therapy is increasingly recognised as a potential approach against antibiotic-resistant infections. Analogous to the rise of antibiotic resistance, bacteria can also evolve phage resistance, a process that frequently entails fitness costs. In this study, a new lytic Pseudomonas aeruginosa phage (Henu5) was isolated and characterised. Henu5 was classified within the Caudoviricetes class and displayed good biological characteristics. The Henu5 genome possesses 92,558 bp of linear dsDNA and a GC content of 49.36%. Additionally, three phage-resistant mutants, R3, R6 and R14, were isolated and investigated for adaptive trade-offs. Compared to wild-type, the phage-resistant mutants mostly exhibited fitness costs in growth, altered morphology, impaired adsorption, reduced biofilm and pyocyanin production and impaired motility, which was confirmed by transmission electron microscopy, as well as increased susceptibility to various antibiotics. In vivo experiments revealed improved survival, alongside diminished colonisation and pathogenicity. Comparative genomics identified mutations in the genes pilQ (R3 and R14) and pilR (R6), both crucial for type IV pili (T4P) biosynthesis and potentially conferring phage resistance, with additional mutations related to the obtained trade-offs. Transcriptomic and real-time quantitative PCR proved that T4P-related genes, together with the hmgA, galU, wzy, fliG, pslA, mexH and exoY genes, were downregulated in all resistant mutants, while the…
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