Fig. 7. BVAB species distinctively contribute to inflammation and physicochemical attributes of epithelial barrier in a human 3D cervical model.

A. vaginae and S. amnii impact arginine and citrulline metabolism, which leads proinflammatory signaling via nitric oxide production (a). S. amnii also induce production of oxidative stress-related metabolites (b). S. amnii induce pipecolate associated with the presence of “clue cells” (c). P. bivia can contribute to elevated cervicovaginal pH levels via asparagine degradation and ammonia production (d). BVAB species also can impact physicochemical attributes of epithelial barrier (mucin degradation and collagen remodeling) (e, f). a A schematic of arginine/citrulline metabolism pathways. Colored circles indicate enriched or depleted metabolites following monoinfection with specific BVAB or infection with the polymicrobial cocktail. a–f Floating bar graphs shows relative intensity of polyamines in 3D cell culture supernatants following bacterial colonization. The relative intensities of metabolites are shown as floating bar graphs. The boxes represent the median and interquartile range and whiskers range from minimum to maximum values. A plus sign (+) on plots indicates mean values. Significant differences between mean intensities of metabolites among infections were corrected for multiple comparisons. p and q values are indicated by ^(p < 0.05, q > 0.01), *(p < 0.05, q < 0.01), **(p < 0.01, q < 0.01), ***(p < 0.001, q < 0.01), ****(p < 0.0001, q < 0.01).