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Staphylococcus aureus is a common human pathogenic bacteria that can cause serious infections, including lethal staphylococcal pneumonia. The development of antimicrobial resistance has limited treatment options for this pathogen; consequently, novel antibiotics and strategies are urgently desired to combat these infections. In recent years, virulence factors secreted by pathogenic microorganisms have been developed as targets for drug discovery. Alpha-hemolysin, a pore-forming cytotoxin that is secreted by most S. aureus strains, is essential for the pathogenesis of S. aureus pneumonia. In this study, we report that apigenin, a compound extracted from parsley that has no antimicrobial activity vs. S. aureus in vitro, can remarkably decrease the production of α-hemolysin at low concentrations. When added to the A549 cells and S. aureus co-culture system, apigenin protected A549 cells from α-hemolysin-mediated injury. Furthermore, in vivo tests indicated that apigenin alleviated injury of the lung tissue and decreased cytokine levels in the bronchoalveolar lavage fluid in the mouse model of S. aureus pneumonia. [ABSTRACT FROM AUTHOR]

α-Hemolysin (Hla) is a self-assembling, channel-forming toxin that is secreted by Staphylococcus aureus and is central to the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections in animal models. In this study, we report that baicalin (BAI), a natural compound that lacks anti–S. aureus activity, could inhibit the hemolytic activity of Hla. Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that BAI binds to the binding sites of Y148, P151, and F153 in the Hla. This binding interaction inhibits heptamer formation. Furthermore, when added to S. aureus cultures, BAI prevents Hla-mediated human alveolar epithelial (A549) cell injury. In vivo studies further demonstrated that BAI protects mice from S. aureus pneumonia. These findings indicate that BAI hinders the cell lysis activity of Hla through a novel mechanism of interrupting the formation of heptamer, which may lead to the development of novel therapeutics that aim against S. aureus Hla. [ABSTRACT FROM AUTHOR]

S taphylococcus aureus is a versatile pathogen that can cause life-threatening infections. The growing emergence of methicillin-resistant S . aureus strains and a decrease in the discovery of new antibiotics warrant the search for new therapeutic targets to combat infections. S taphylococcus aureus produces many extracellular virulence factors that contribute to its pathogenicity. Therefore, targeting bacterial virulence as an alternative strategy to the development of new antimicrobials has gained great interest. α-Toxin is a 33.2-k Da, water-soluble, pore-forming toxin that is secreted by most S . aureus strains. α-Toxin is essential for the pathogenesis of pneumonia, as strains lacking α-toxin display a profound defect in virulence. In this report, we demonstrate that isoalantolactone ( IAL), a naturally occurring compound found in I nula helenium ( Compositae), has no anti- S . aureus activity as per MIC evaluation in vitro. However, IAL can markedly inhibit the expression of α-toxin in S . aureus at very low concentrations. Furthermore, the in vivo data indicate that treatment with IAL protects mice from S . aureus pneumonia. [ABSTRACT FROM AUTHOR]