Frontiers in Cellular and Infection Microbiology (Mar 2024)

Phage P2-71 against multi-drug resistant Proteus mirabilis: isolation, characterization, and non-antibiotic antimicrobial potential

  • Zhiyou Dong,
  • Ruihu Wu,
  • Lijuan Liu,
  • Shengquan Ai,
  • Jinpeng Yang,
  • Qianlan Li,
  • Keyi Fu,
  • Yunian Zhou,
  • Hualin Fu,
  • Ziyao Zhou,
  • Haifeng Liu,
  • Zhijun Zhong,
  • Xianmeng Qiu,
  • Guangneng Peng

DOI
https://doi.org/10.3389/fcimb.2024.1347173
Journal volume & issue
Vol. 14

Abstract

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Proteus mirabilis, a prevalent urinary tract pathogen and formidable biofilm producer, especially in Catheter-Associated Urinary Tract Infection, has seen a worrying rise in multidrug-resistant (MDR) strains. This upsurge calls for innovative approaches in infection control, beyond traditional antibiotics. Our research introduces bacteriophage (phage) therapy as a novel non-antibiotic strategy to combat these drug-resistant infections. We isolated P2-71, a lytic phage derived from canine feces, demonstrating potent activity against MDR P. mirabilis strains. P2-71 showcases a notably brief 10-minute latent period and a significant burst size of 228 particles per infected bacterium, ensuring rapid bacterial clearance. The phage maintains stability over a broad temperature range of 30-50°C and within a pH spectrum of 4-11, highlighting its resilience in various environmental conditions. Our host range assessment solidifies its potential against diverse MDR P. mirabilis strains. Through killing curve analysis, P2-71’s effectiveness was validated at various MOI levels against P. mirabilis 37, highlighting its versatility. We extended our research to examine P2-71’s stability and bactericidal kinetics in artificial urine, affirming its potential for clinical application. A detailed genomic analysis reveals P2-71’s complex genetic makeup, including genes essential for morphogenesis, lysis, and DNA modification, which are crucial for its therapeutic action. This study not only furthers the understanding of phage therapy as a promising non-antibiotic antimicrobial but also underscores its critical role in combating emerging MDR infections in both veterinary and public health contexts.

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