Contribution of rsaC, a small non-coding RNA, towards the pathogenicity of Staphylococcus aureus in a mouse systemic infection model

Understanding how a pathogen responds to the host stimuli and succeeds in causing disease is crucial for developing a novel treatment approach against the pathogen. Transcriptomic analysis facilitated by RNA-Seq technologies is used to examine bacterial responses at the global level. However, the ability to understand pathogen behavior inside the host tissues is hindered by much lower pathogen biomass than host tissue. Recently, we succeeded in establishing a method to enrich Staphylococcus aureus cells from infected organs. In this research, we analyzed the small non-coding RNA (sRNA) transcriptome of S. aureus inside the host and found that rsaC was among the highly expressed sRNAs. Furthermore, by gene disruption and complementation, we demonstrated that rsaC was required for full pathogenicity of S. aureus in a murine model. Besides, we found that {Delta}rsaC showed a difference in gene expression depending on the oxygen and host stress. The findings of this study suggest rsaC acts as a novel virulence factor in S. aureus and might facilitate the adaptation of staphylococci within the host. ImportanceDrug-resistant Staphylococcus aureus is among the pathogen for which new treatment options are urgently needed. However, limited understanding of S. aureus pathogenesis in the host has hindered unearthing potential strategies to treat the infections. Here, based on the in vivo transcriptomic analysis, we present the identification of a small non-coding RNA (sRNA) rsaC as a novel virulence factor of S. aureus. Furthermore, we performed transcriptomic analysis of the rsaC disrupted mutant and identified different pathways, possibly controlled by rsaC, during aerobic, anaerobic, and in vivo conditions. These findings contribute to reveal the role of sRNA rsaC and broadens our understanding of the adaptation of S. aureus to host environments.