Stable Neutralization of a Virulence Factor in Bacteria Using Temperate Phage in the Mammalian Gut.

ABSTRACT: Elimination or alteration of select members of the gut microbiota is key to therapeutic efficacy. However, the complexity of these microbial inhabitants makes it challenging to precisely target bacteria. Here, we deliver exogenous genes to specific bacteria by genomic integration of temperate phage for long-lasting modification. As a real-world therapeutic test, we engineered λ phage to transcriptionally repress Shiga toxin by using genetic hybrids between λ and other lambdoid phages to overcome resistance encoded by the virulence-expressing prophage. We show that a single dose of engineered phage propagates throughout the bacterial community and reduces Shiga toxin production in an enteric mouse model of infection without markedly affecting bacterial concentrations. Our work reveals a new

SUBMITTER: Hsu BB 

PROVIDER: S-EPMC6989128 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature