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<p>Biliary tract infections (BTIs) arise within a bile-rich environment that profoundly shapes microbial ecology and pathogen adaptation. <i>Pseudomonas aeruginosa</i>, a major opportunistic pathogen in nosocomial settings, exhibits remarkable physiological plasticity, that enable persistence in such challenging niches. However, the influence of bile on <i>P. aeruginosa</i>’s adaptive responses and phage–host interactions remains largely unexplored. Here, we demonstrate that ox-bile imposes concentration-dependent stress on <i>P. aeruginosa</i> strain ZS-PA-35, indicative of host-derived selective pressure. Notably, ox-bile enhances biofilm formation and promotes swarming and twitching motilities while concurrently suppressing swimming motility. Moreover, ox-bile modulates phage susceptibility, likely through altered receptor expression: exposure to ox-bile sensitizes <i>P. aeruginosa</i> to the type IV pili (T4P)-dependent phage phipa2, whereas susceptibility to the lipopolysaccharide (LPS)-targeting phage phipa10 remains unchanged. Genome-wide mutagenesis identified resistance-conferring mutations affecting T4P structures, LPS biosynthesis, and associated regulatory pathways. Among these, phage-resistant mutants Δ<i>pilT</i> and Δ<i>galU</i> retained high fitness under ox-bile stress, accompanied by enhanced swarming and swimming motilities. Furthermore, in a lysogenic context, ox-bile markedly suppressed prophage accumulation in the T4P-dependent strain ZS-PA-05. These findings reveal that bile acts as a critical environmental cue shaping both adaptive physiology and phage susceptibility in <i>P. aeruginosa</i>, with broad implications for microbiome dynamics and the development of phage-based therapies targeting bile-impacted infections.</p>

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Bile modulates phage–host interactions in multidrug-resistant Pseudomonas aeruginosa

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月17日

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  • Muhammad Saleem Iqbal Khan,
  • Ju Wu,
  • Shuangshuang Hou,
  • Shenlin Ji,
  • He Li,
  • Yaoyuan Chang,
  • Bingrui Sui,
  • Demeng Tan,
  • Jiajun Yin

摘要

Biliary tract infections (BTIs) arise within a bile-rich environment that profoundly shapes microbial ecology and pathogen adaptation. Pseudomonas aeruginosa, a major opportunistic pathogen in nosocomial settings, exhibits remarkable physiological plasticity, that enable persistence in such challenging niches. However, the influence of bile on P. aeruginosa’s adaptive responses and phage–host interactions remains largely unexplored. Here, we demonstrate that ox-bile imposes concentration-dependent stress on P. aeruginosa strain ZS-PA-35, indicative of host-derived selective pressure. Notably, ox-bile enhances biofilm formation and promotes swarming and twitching motilities while concurrently suppressing swimming motility. Moreover, ox-bile modulates phage susceptibility, likely through altered receptor expression: exposure to ox-bile sensitizes P. aeruginosa to the type IV pili (T4P)-dependent phage phipa2, whereas susceptibility to the lipopolysaccharide (LPS)-targeting phage phipa10 remains unchanged. Genome-wide mutagenesis identified resistance-conferring mutations affecting T4P structures, LPS biosynthesis, and associated regulatory pathways. Among these, phage-resistant mutants ΔpilT and ΔgalU retained high fitness under ox-bile stress, accompanied by enhanced swarming and swimming motilities. Furthermore, in a lysogenic context, ox-bile markedly suppressed prophage accumulation in the T4P-dependent strain ZS-PA-05. These findings reveal that bile acts as a critical environmental cue shaping both adaptive physiology and phage susceptibility in P. aeruginosa, with broad implications for microbiome dynamics and the development of phage-based therapies targeting bile-impacted infections.