Fig. 5: Anti-phage immunity reduces effectiveness of phage treatment.
A Schematic of murine model of phage treatment targeting VRE colonization after preexposure to phage to induce anti-phage immunity. Mice were given either a course of phage cocktail or vehicle control. Two weeks later mice were administered vancomycin in drinking water. After 7 days on antibiotic water, mice were inoculated with VRE by oral gavage. Seven days after VRE exposure, mice were then treated for 7 days with either ɸCT or vehicle control administered by IP injection. Stool was collected from mice and assessed for presence of (B) VRE and (C) phage throughout the course of the study. D–G Tissues were collected and plated to enumerate lytic phage at day 13.SI = small intestine LI = large intestine. Serum was then used to probe anti-phage antibody production (H–L) with (M) IgG titers for double cocktail treatment shown calculated from IC50 from H–L. N Serum was also collected at day 13 and tested for phage neutralizing activity. Parametric data is shown as geometric mean with 95% confidence interval (5 M), while non-parametric data is displayed as median with interquartile range (5B-L, 5 N). Data are representative of two (D–G) or three (B, C, H–L) experiments with n = 5 per group. For (B, C), a mixed-effects analysis was used to compare the three groups with repeated measures. To compare groups in (D–G), Mann–Whitney test was used and shown as geometric mean with 95% confidence interval. Statistical tests for (M) include two-way ANOVA with Holm–ŠÃdák multiple comparisons test. Asterix (*) refers to statistical comparisons between groups represented by purple circles and orange squares. Dollar sign ($) compares between green triangles and orange squares and hashtag (#) compares purple circles and green triangles. To indicate significance, one symbol p < 0.01, two symbols p < 0.001, three symbols p < 0.0001. Source data are provided as a Source Data file.
