Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternatives. However, phage-mediated killing is often limited by bacterial resistance development (1,2). 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 a phage-based companion diagnostic (3), 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.
1
The categories of this paper are: bioinformatics
8
The categories of this paper are: genomics
12
The categories of this paper are: behavior
10
The categories of this paper are: and
29
The categories of this paper are: education
16
The categories of this paper are: microbiology
5
The categories of this paper are: cell
17
The categories of this paper are: molecular
2
The categories of this paper are: biology
23
The categories of this paper are: immunology
22
The categories of this paper are: physiology
19
The categories of this paper are: epidemiology
21
The categories of this paper are: toxicology
6
The categories of this paper are: plant
15
The categories of this paper are: developmental
32
The categories of this paper are: zoology