Dual transcriptomic profiling of Staphylococcus aureus endocarditis in a porcine model reveals strong parallels with...

Understanding the intricate interactions between Staphylococcus aureus and valve cells during the course of endocarditis is crucial for developing more effective treatments for an infection that has a mortality rate exceeding 30%. To investigate the molecular adaptations occurring in both the valve tissue and bacteria during infection, we performed dual RNA-seq analysis on valves from patients undergoing valve replacement surgery due to S. aureus endocarditis as well as from an experimental pig model of the disease. The results revealed remarkably consistent expression profiles between human and pig samples, characterized by endothelial damage and the activation of valve interstitial cells, leading to excessive inflammation, heightened coagulation cascades, collagen degradation, and extracellular matrix remodeling. Additionally, transcriptional profiling of S. aureus on infected valves showed the upregulation of genes involved in iron acquisition, capsule synthesis, protease production, and adhesin formation, along with downregulation of genes associated with pyrimidine metabolism and nitrate reduction. These findings provide a detailed map of the transcriptional landscape defining both the infected valve tissue and S. aureus during active endocarditis.

To gain a full understanding of how bacteria infect tissues, it is necessary to characterize both the bacteria and the tissue at the time of infection. However, this analysis is very complex because it involves obtaining infected tissue directly from patients and analyzing it with minimal processing to preserve the characteristics of the natural state of infection. In this study, we examined the gene expression profiles of replaced heart valves from patients with Staphylococcus aureus infection and compared them with pig valves experimentally infected with the same bacteria. Our findings provide a detailed insight into the changes occurring in the infected tissue and the bacterial adaptations required for multiplication and survival on the valve tissue. Notably, the strong similarity observed between human and porcine valves confirms that the porcine endocarditis model closely mirrors the human condition, making it a valuable tool for testing new therapies against this serious infection.