Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice

Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR-Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most…

• WT
  Wellcome Trust
• CA
  Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator

  Award: IDSEP160030
• BA
  Biomedical Advanced Research and Development Authority

  Award: IDSEP160030