Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors.

ABSTRACT: Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternative antimicrobials. However, phage-mediated killing is often limited by bacterial resistance development. Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using phage-based companion diagnosti

SUBMITTER: Du J 

PROVIDER: S-EPMC10359290 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature