Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning

ABSTRACTThe virulence factors of Staphylococcus aureus are tightly controlled by two-component systems (TCSs) and small RNA (sRNA). TCSs have been well studied over the past several decades, but our understanding of sRNA functions lags far behind that of TCS functions. Here, we studied the biological role of sRNA from 506 S. aureus RNA-seq datasets using independent component analysis (ICA). We found that a previously neglected sRNA, Sau-41, functions in the Agr system. Sau-41 is located within the PSMα operon and controlled by the Agr system. It was predicted to share 22-base complementarity with RNAIII, a major regulator of S. aureus virulence. The EMSA results demonstrated that Sau-41 directly binds to RNAIII. Furthermore, our results found that Sau-41 is capable of repressing S. aureus haemolysin activity by downregulating α-haemolysin and δ-toxin. The repression of α-haemolysin was attributed to the competition between the 5’ UTR of hla and Sau-41 for binding RNAIII. We observed that Sau-41 mitigated S. aureus virulence in an orthopaedic implant infection mouse model and alleviated osteolysis. Together, our results indicate that Sau-41 is a virulence-regulating RNA and suggest that Sau-41 might be involved in a negative feedback mechanism to control the Agr system. This work is a demonstration of using ICA in sRNA identification by mining high-throughput data and could be extended to other organisms as well

Chiral Supramolecular Hydrogel Loaded with Dimethyloxalyglycine to Accelerate Chronic Diabetic Wound Healing by Promoting Cell Proliferation and Angiogenesis

Chronic refractory wounds are one of the most serious complications of diabetes, and the effects of common treatments are limited. Chiral hydrogel combined with dimethyloxalyglycine (DMOG) as a dressing is a promising strategy for the treatment of chronic wounds. In this research, we have developed a DMOG-loaded supramolecular chiral amino-acid-derivative hydrogel for wound dressings for full-thickness skin regeneration of chronic wounds. The properties of the materials, the ability of sustained release drugs, and the ability to promote angiogenesis were tested in vitro, and the regeneration rate and repair ability of full-thickness skin were tested in vivo. The chiral hydrogel had the ability to release drugs slowly. It can effectively promote cell migration and angiogenesis in vitro, and promote full-thickness skin regeneration and angiogenesis in vivo. This work offers a new approach for repairing chronic wounds completely through a supramolecular chiral hydrogel loaded with DMOG