Fig. 7: Synthetic EcN outfitted with modified T0SS exhibits superior therapeutic efficacy in treating hyperuricemic mice and detoxifying human serum samples.
From: Oral delivery of therapeutic proteins by engineered bacterial type zero secretion system
a Experimental design of UA- and PO-induced murine model of hyperuricemia as well as treatment procedures. Mice fed a normal diet and intraperitoneally injected with vehicle are indicated as “Con”. Hyperuricemic mice were induced via a UA-supplemented diet (2% UA in the diet) and daily intraperitoneal injection of 250 mg/kg PO for 4 weeks. At the onset of hyperuricemia induction, hyperuricemic mice were gavaged with saline (abbreviated as “UA”), EcN (abbreviated as “UA + E”), EcN∆thyA-SUT (abbreviated as “UA + T”) or EcN∆nlpI∆thyA-SU (abbreviated as “UA + O”) (n = 6). b–e Serum UA (b), urine UA (c), serum CRE (d) and IL-1β (e) were measured. (n = 6 mice) (f) Representative histopathological images of colon slices obtained from five groups of mice. The slices were stained with hematoxylin and eosin (H&E). The black arrow indicates infiltration of immune cells, and the red arrow indicates sloughed-off epithelial cells. Scale bar = 50 μm. g, h The UA (g) and glucose (h) degradation efficacy of Uox-loaded OMVs derived from EcN∆nlpI∆thyA-SU on serum samples from hyperuricemic patients, in response to OMV treatment for 30 min (n = 9 biologically independent samples). i, j Lactic acid (i) and glucose (j) degradation efficacy of Lox-loaded OMVs derived from EcNΔnlpI-OL on serum samples from lung cancer patients (n = 7 biologically independent samples), in response to OMV treatment for 30 min. Data are presented as the mean ± SD. The P value was determined by one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons test (b–e) or a two-tailed paired t test (g–j). Source data are provided as a Source Data file.
