Fig. 2: Testosterone and DHT stimulate agr quorum sensing and drive S. aureus pathogenesis.
From: Skin androgens regulate Staphylococcus aureus pathogenicity via quorum sensing
a, The S. aureus HG003 strain was treated with 10 nM testosterone or vehicle to early-log phase (OD600 = 0.4). Volcano plot showing genes with >4-fold expression change (green) by RNA sequencing. b, Schematic of S. aureus agr quorum-sensing system. c, agr-induced bioluminescence of HG003agr-P3::lux quorum-sensing reporter in vivo treated with 10 nM testosterone, DHT, AIP-I or vehicle (n = 3). Means ± s.e.m. (error bars) are plotted. #P < 0.0001 by 2-way ANOVA compared with vehicle. d, Quantitative real-time PCR (qRT-PCR) of S. aureus HG003 (type-I strain) treated with 10 nM testosterone, AIP-I or vehicle (n = 3) until mid-exponential growth (OD600 = 0.6). Gene expression is normalized to gyrA. Means ± s.e.m. (error bars) are plotted. **P < 0.01, ***P < 0.001 by unpaired 2-tailed Student’s t-test. e,f, qRT-PCR of MRSA type-II (USA100) (e) and MRSA type-III (MW2) (f) strains cultured to mid-log phase, treated with 10 nM testosterone, AIP-II or AIP-III (n = 3). psmα expression is normalized to gyrA. Means ± s.e.m. (error bars) are plotted. *P < 0.05 by unpaired 2-tailed Student’s t-test. g, qRT-PCR for psmα in S. aureus isolates from patients with AD30 treated with 10 nM testosterone or vehicle (n = 3) to mid-exponential growth. Means ± s.e.m. (error bars) are plotted. *P < 0.05, **P < 0.01 by unpaired 2-tailed Student’s t-test. h, Percentage of S. aureus-induced RBC haemolysis with and without 10 nM testosterone, DHT or AIP-I (n = 4 human donors, 2 men and 2 women). Means ± s.e.m. (error bars) are plotted. ****P < 0.0001, by 1-way ANOVA. i, Percentage of S. aureus-induced skin cell cytotoxicity with and without 10 nM testosterone, AIP-I or AIP-I and testosterone (n = 3). Means ± s.e.m. (error bars) are plotted. **P < 0.01, ***P < 0.001 by 1-way ANOVA. j, agr-induced bioluminescence in vivo. Left, epicutaneous infection of male and female Hsd3b6fl/fl (n = 7 males and n = 5 females) and Hsd3b6∆skin mice (n = 6 males and n = 5 females) with bioluminescent CA-MRSA-agr-P3::lux with agr-induced bioluminescence quantified over time. Right, representative bioluminescence images. $P < 0.0001, **P < 0.01 and non-significant (NS) by 2-way ANOVA with comparisons. Aggregate of two experiments. Means ± s.e.m. (error bars) are plotted. See Extended Data Figs. 4–6. Panel b created in BioRender; Harris, T. https://biorender.com/wd041bk (2025).
