<p>The rise of multidrug-resistant (MDR) extraintestinal pathogenic <i>Escherichia coli</i> (ExPEC) poses a severe healthcare threat, necessitating alternative treatment strategies such as bacteriophage therapy. In this study, four lytic phages (EC.W2-9, EC.W5-4, EC.W8-1, and EC.W14-2) were isolated from hospital wastewater and characterized for their efficacy against MDR ExPEC isolates. A total of 44 ExPEC isolates were analyzed, with 41% belonging to sequence type (ST) 131 and 59% to ST410, all exhibiting MDR phenotypes. Among these, 49% produced extended-spectrum <i>β</i>-lactamases (ESBLs), and 86% were identified as carbapenem-resistant <i>E. coli</i> (CREC). Phages EC.W2-9, EC.W8-1, and EC.W14-2 displayed high lytic activity against ST131 (≥ 90% lysis) but were significantly less effective against ST410 (≤ 30% lysis). Phage EC.W5-4 exhibited intermediate efficacy, lysing 78% of ST131 and 23% of ST410 isolates. Morphological and phylogenetic analyses classified EC.W2-9, EC.W5-4, and EC.W14-2 within the <i>Tequatrovirus</i> genus of the <i>Straboviridae</i> family, while EC.W8-1 belonged to the <i>Kuravirus</i> genus of the <i>Podoviridae</i> family. These phages demonstrated favorable biological properties, including short latent periods (10–25&#xa0;min), high burst sizes (115–158 pfu/cell), and stability across a broad temperature (≤ 70&#xa0;°C) and pH range (3–10). Genomic analysis (46,328–116,943&#xa0;bp, 35.2–39.9% G + C content) confirmed the absence of virulence and antibiotic resistance genes. Furthermore, combined phage therapy effectively reduced planktonic and biofilm growth of MDR-ExPEC. These findings demonstrate the potential of these phages as effective therapeutic agents against MDR ExPEC, particularly ST131 and ST410, in combating antibiotic-resistant infections.</p>

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Characterization and genome analyses of the novel phages targeting extraintestinal Escherichia coli clones ST131 and ST410

  • Md Shamsuzzaman,
  • Yoon-Jung Choi,
  • Shukho Kim,
  • Jungmin Kim

摘要

The rise of multidrug-resistant (MDR) extraintestinal pathogenic Escherichia coli (ExPEC) poses a severe healthcare threat, necessitating alternative treatment strategies such as bacteriophage therapy. In this study, four lytic phages (EC.W2-9, EC.W5-4, EC.W8-1, and EC.W14-2) were isolated from hospital wastewater and characterized for their efficacy against MDR ExPEC isolates. A total of 44 ExPEC isolates were analyzed, with 41% belonging to sequence type (ST) 131 and 59% to ST410, all exhibiting MDR phenotypes. Among these, 49% produced extended-spectrum β-lactamases (ESBLs), and 86% were identified as carbapenem-resistant E. coli (CREC). Phages EC.W2-9, EC.W8-1, and EC.W14-2 displayed high lytic activity against ST131 (≥ 90% lysis) but were significantly less effective against ST410 (≤ 30% lysis). Phage EC.W5-4 exhibited intermediate efficacy, lysing 78% of ST131 and 23% of ST410 isolates. Morphological and phylogenetic analyses classified EC.W2-9, EC.W5-4, and EC.W14-2 within the Tequatrovirus genus of the Straboviridae family, while EC.W8-1 belonged to the Kuravirus genus of the Podoviridae family. These phages demonstrated favorable biological properties, including short latent periods (10–25 min), high burst sizes (115–158 pfu/cell), and stability across a broad temperature (≤ 70 °C) and pH range (3–10). Genomic analysis (46,328–116,943 bp, 35.2–39.9% G + C content) confirmed the absence of virulence and antibiotic resistance genes. Furthermore, combined phage therapy effectively reduced planktonic and biofilm growth of MDR-ExPEC. These findings demonstrate the potential of these phages as effective therapeutic agents against MDR ExPEC, particularly ST131 and ST410, in combating antibiotic-resistant infections.