Fig. 2: Putative l-ornithine oxidative degradation locus consistently differentially expressed in gnotobiotic models for Cd metabolism in a non-inflamed environment.
From: Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization
a, Hypervirulent WT Cd R20291 elicits a significantly greater magnitude of pathology in the cecal blind tip and proximal colon of mice than all other groups, including WT Cd 630. Both WT infections (630 and R20291) incite significantly higher pathology than all Tox− and uninfected control (crtl) groups, which do not differ from one another (one-way analysis of variance (ANOVA) F(5,22) = 180.3 with Tukey’s post hoc comparisons. WT 630 versus R20291 Tox− and control group, P < 0.0001; WT R20291 versus 630 Tox− and control group, P < 0.0001; n = 5 mice per group except for the 630 uninfected control where n = 4; bars denote mean ± s.e.m.). b, Histopathological score breakdown for mice infected with WT R20291 or WT 630. R20291 leads to a significantly higher level of inflammatory cell infiltration (multiple unpaired Student’s t-tests with Benjamini, Krieger, Yekutieli two-stage linear step-up procedure; n = 5 mice per group; bars denote mean ± s.e.m.). c, Extent of differential gene expression between WT and Tox− Cd across different gnotobiotic settings (DESeq2 Wald test). DC1 (n = 5 WT, n = 4 Tox−); DC2 (630, n = 4 mice per group; R20291, n = 5 mice per group). d, Combined differential gene expression between 630 WT (positive fold change) and 630 Tox− (negative) combined across both defined communities (adjusted P value < 0.01, n = 9 WT, n = 8 Tox−). e, Normalized expression values (reads per kilobase million) of a putative l-ornithine degradation locus, the only genomic locus consistently differentially expressed across Cd strains and two different defined communities (box-plots denote interquartile range, whiskers denote min to max). f, Schematic of the ornithine oxidative degradation pathway; l-ornithine undergoes racemization to d-ornithine (orr, ornithine racemase), migration of the amino group from C5 to C4 (oraSoraE, d-ornithine aminomutase), a dehydrogenase reaction generating ammonia (ord, 2,4-diaminopentanoate dehydrogenase), CoA-mediated thiolytic cleavage generating acetyl-CoA (ortAortB, 2-amino-4-ketopentanoate thiolase) leading to ATP production via acetyl phosphate.
