Longistylin A inhibited SaeRS-dependent hemolysin expression and activated Type VII secretory system of Staphylococcus aureus.

To maintain cellular homeostasis under the stresses, bacteria always initiate various responses. The transcriptomic profiles of S. aureus treated with longistylin A were assessed by RNA-sequencing. A total of 2585 genes were identified. KEGG analysis enriched differentially expressed genes (DEGs) in different physiological processes. Two-component system and bacterial infection metabolisms, the most significant enrichment pathways, were downregulated by longistry A. The SaeRS two-component system is essential for the hemolytic activity and virulence in S. aureus. SarT is a repressor of alpha-hemolysin (Hla) in S. aureus. Transcriptome data shows that the expression of genes encoding gama-hemolysin components and SaeRS two-component system were inhibited under the treatment of LGA, while the expression of SarT is increased. The Type VII secretory system (T7SS) is responsible for the secretion of virulence factors. Longistry A dramatically upregulated the expression of T7SS related genes, such as essB and esaC. LGA did not affect intracellular Hla accumulation. The downregulation of hemolysin-related genes and upregulation of T7SS related genes may be due to the feedback regulation of inhibited hemolysin secretion caused by longistry A treatment. Overall, longistry A inhibited hemolysin secretion by targeting cell membrane phospholipids, thereby inhibited SaeRS-dependent hemolysin expression and activated Type VII secretory system. Overall design: S. aureus ATCC 6538 were treated with 0 or 4 µg/mL of longistry A for 4 h and collected for total RNA isolation.