Therapeutic and Diagnostic Potential of a Novel K1 Capsule Dependent Phage, JSSK01, and Its Depolymerase in Multidrug-Resistant Escherichia coli Infections

Int J Mol Sci. 2024 Nov 21;25(23):12497. doi: 10.3390/ijms252312497.

Abstract

Bacteriophages are viruses that have the potential to combat bacterial infections caused by antimicrobial-resistant bacterial strains. In this study, we investigated a novel lytic bacteriophage, vB_EcoS_JSSK01, isolated from sewage in Hualien, Taiwan, which effectively combats multidrug-resistant (MDR) Escherichia coli of the K1 capsular type. K1 E. coli is a major cause of severe extraintestinal infections, such as neonatal meningitis and urinary tract infections. Phage JSSK01 was found to have a genome size of 44,509 base pairs, producing approximately 123 particles per infected cell in 35 min, and was highly stable across a range of temperatures and pH. JSSK01 infected 59.3% of the MDR strains tested, and its depolymerase (ORF40) specifically degraded the K1 capsule in these bacteria. In a zebrafish model, JSSK01 treatment after infection significantly improved survival, with survival in the treated group reaching 100%, while that in the untreated group dropped to 10% after three days. The functional activity of depolymerase was validated using zone inhibition and agglutination tests. These results indicate that JSSK01 and its substrate-specific depolymerase have promising therapeutic and diagnostic applications against K1-encapsulated MDR E. coli infections.

Keywords: Escherichia coli; K1 capsule; depolymerase; endo-N-acetylneuraminidase; multidrug resistance; phage therapy.

MeSH terms

  • Animals
  • Antigens, Bacterial
  • Bacterial Capsules / metabolism
  • Bacteriophages / genetics
  • Drug Resistance, Multiple, Bacterial* / genetics
  • Escherichia coli Infections* / drug therapy
  • Escherichia coli Infections* / microbiology
  • Escherichia coli* / drug effects
  • Escherichia coli* / genetics
  • Humans
  • Phage Therapy
  • Polysaccharides, Bacterial
  • Zebrafish*

Substances

  • capsular polysaccharide K1
  • Antigens, Bacterial
  • Polysaccharides, Bacterial