Department of Bacteriology and Virology, School of Medicine, Isfahan University of Medical Sciencesgrid.411036.1, Isfahan, Iran.
Department of Biosystems, KU Leuven, Leuven, Belgium.
Microbiol Spectr. 2022 Oct 26;10(5):e0209222. doi: 10.1128/spectrum.02092-22. Epub 2022 Oct 4.
Proteus mirabilis is a biofilm-forming bacterium and one of the most common causes of catheter-associated urinary tract infections (CAUTIs). The rapid spread of multidrug-resistant P. mirabilis represents a severe threat to management of nosocomial infections. This study aimed to isolate a potent phage cocktail and assess its potential to control urinary tract infections caused by biofilm-forming P. mirabilis. Two lytic phages, Isf-Pm1 and Isf-Pm2, were isolated and characterized by proteome analysis, transmission electron microscopy, and whole-genome sequencing. The host range and effect of the phage cocktail to reduce the biofilm formation were assessed by a cell adhesion assay in Vero cells and a phantom bladder model. The samples treated with the phage cocktail showed a significant reduction (65%) in the biofilm mass. Anti-quorum sensing and quantitative real-time PCR assays were also used to assess the amounts of transcription of genes involved in quorum sensing and biofilm formation. Furthermore, the phage-treated samples showed a downregulation of genes involved in the biofilm formation. In conclusion, these results highlight the efficacy of two isolated phages to control the biofilms produced by P. mirabilis CAUTIs. The rapid spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial strains and biofilm formation of bacteria have severely restricted the use of antibiotics and become a challenging issue in hospitals. Therefore, there is a necessity for alternative or complementary treatment measures, such as the use of virulent bacteriophages (phages), as effective therapeutic strategies.
奇异变形杆菌是一种生物膜形成菌，也是导致导管相关尿路感染（CAUTI）的最常见原因之一。多药耐药奇异变形杆菌的迅速传播对医院感染管理构成了严重威胁。本研究旨在分离一种有效的噬菌体鸡尾酒，并评估其控制生物膜形成奇异变形杆菌引起的尿路感染的潜力。通过蛋白质组分析、透射电子显微镜和全基因组测序，分离并鉴定了两种裂解噬菌体 Isf-Pm1 和 Isf-Pm2。通过在vero 细胞和幻影膀胱模型中进行细胞黏附试验，评估噬菌体鸡尾酒的宿主范围和减少生物膜形成的效果。与未处理的生物膜相比，用噬菌体鸡尾酒处理的样本的生物膜质量显著减少（65%）。还使用群体感应抑制和实时定量 PCR 检测来评估与群体感应和生物膜形成相关的基因转录量。此外，噬菌体处理的样本中与生物膜形成相关的基因表达下调。综上所述，这些结果突出了两种分离噬菌体控制 CAUTI 中奇异变形杆菌生物膜形成的功效。多药耐药（MDR）和广泛耐药（XDR）细菌菌株的迅速传播以及细菌生物膜的形成严重限制了抗生素的使用，成为医院的一个挑战问题。因此，需要替代或补充治疗措施，如使用毒性噬菌体（噬菌体）作为有效的治疗策略。
