Fig. 4: CadD contributes to GBS pathogenesis and cognate disease outcomes associated with infection.

A Experimental design. Animals were harem mated and pregnancy was confirmed at embryonic day 0.5 by the presence of a mucus plug (E0.5). At embryonic day 13.5 (E13.5) animals were infected intravaginally with GBS. B Healthy pregnancy at 2 days post-infection vs. C premature rupture of membranes (PPROM) and D intrauterine hemorrhage at 2 days post-infection as a consequence of GBS infection. Analyses of percent animals E without PPROM or preterm birth (PTB) or F maternal survival. Dotted line indicates term for the average gestation in the C57BL6/J mouse model used in this study. n = 12 animals in the uninfected control group and 15 animals in the experimental groups. Infection with WT GB112 resulted in significant increases in PPROM and preterm birth (E) as well as maternal mortality (F) as determined by Mantel–Cox log-rank test (**P = 0.0024) and Gehan–Breslow–Wilcoxon test (**P = 0.0067). Animals infected with the ∆cadD mutant experienced no observable PPROM, preterm birth or maternal mortality and were statistically indistinguishable from uninfected controls, a result that was reversed via genetic complementation (PPROM/PTB: Mantel–Cox log-rank test (*P = 0.0151) and Gehan–Breslow–Wilcoxon test *P = 0.0422 (E); maternal mortality: Mantel–Cox log-rank test (*P = 0.0147) and Gehan–Breslow–Wilcoxon test *P = 0.0339; compared to uninfected animals) (F).