Skin surface Testosterone regulate S. aureus pathogenesis through activation of agr quorum sensing

The goal of the study is to assess the impact of skin androgens on S. aureus pathogenicity.Abstract: Staphylococcus aureus, the most frequent cause of skin infections, is more common in men than women and selectively colonizes the skin during inflammation. Yet, the specific cues that drive infection in these settings remain unclear. Here we show that the host androgens testosterone and dihydrotestosterone promote S. aureus pathogenesis and skin infection. In lower levels of these hormones, skin infection in vivo is limited. We demonstrate that testosterone stimulates the agr quorum sensing system through the agrAC two-component system in a concentration-dependent manner, with the capacity to circumvent other inhibitory signals in the environment. Taken together, our work defines a previously uncharacterized inter-kingdom signal between the skin and the opportunistic pathogen S. aureus and identifies the mechanism of sex-dependent differences in S. aureus skin infection.Experiment details:HG003 strain of S. aureus(NCTC8325) was treated with 10nM,100nM Testosterone, 10nM Pregnenolone(carbon control), and Veh till the mid-log phase. Cells were harvested and RNA samples were collected and sequenced.Raw sequencing reads in fastq format were aligned and annotated to the S. aureus NCTC8325 reference genome.