Bibliographic Details
| Title: |
Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors. |
| Authors: |
Du, Jiemin, Meile, Susanne, Baggenstos, Jasmin, Jäggi, Tobias, Piffaretti, Pietro, Hunold, Laura, Matter, Cassandra I., Leitner, Lorenz, Kessler, Thomas M., Loessner, Martin J., Kilcher, Samuel, Dunne, Matthew |
| Source: |
Nature Communications; 7/20/2023, Issue 1, p1-10, 10p |
| Subject Terms: |
BACTERIOPHAGES, ESCHERICHIA coli, URINARY tract infections, COMPANION diagnostics, DRUG resistance in bacteria, ENGINEERS |
| 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 diagnostics, we identified potential HEPT responder patients and treated their urine ex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patient E. coli bacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials. Du et al. genetically engineer bacteriophages into heterologous effector phage therapeutics, enabling dual phage- and effector-mediated targeting for a two-pronged attack against bacterial pathogens. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
