Extended Data Fig. 8: Enantiomer-testosterone (ent-T) inhibits the expression of RNA III in atopic dermatitis strains of S. aureus and also inhibits S. aureus quorum sensing in male and female mice in vivo.
From: Skin androgens regulate Staphylococcus aureus pathogenicity via quorum sensing
a, qRT-PCR of strains of S. aureus obtained from patients with atopic dermatitis46 and treated with 10 nM or ent-T, a stereoisomer of testosterone (n = 3). Expression of target gene RNAIII normalized to housekeeping gene gyrA expression. Means ± SEM (error bars) are plotted.*p < 0.05 by two-tailed paired t-test. b, Bioluminescence of agr-P3 reporter (HG003agrP3::lux) treated with testosterone, ent-T or testosterone with escalating amounts of ent-T at the same time as testosterone. #p < 0.0001 or ns by two-way ANOVA compared to testosterone alone. c, In silico analysis with testosterone (left) and ent-T (right) bound to a hydrophobic pocket of AgrC bound by the polar residues T141, T197, and S201. Testosterone (left) is predicted to form stable hydrogen bonds with S194 and T190. Ent-T (right)is predicted to bind to the same hydrophobic pocket, but without the equivalent stability of hydrogen-bond interactions. d, Bioluminescence images of Fig. 5g, male wild-type mice epicutaneously infected with 1×106 CFUs CA-MRSA-agr-P3 S. aureus reporter treated with ent-T or vehicle. e, Bioluminescence images of female wild-type mice epicutaneously infected with 1×106 CFUs CA-MRSA-agr-P3 S. aureus reporter treated with testosterone, ent-T, or vehicle, and f, Bioluminescence quantified over time ****p < 0.0001 by two-way ANOVA with comparisons shown. Means ± SEM (error bars) are plotted.
