Norwogonin aids in fighting MRSA-induced pneumonia by targeting agrAC to inhibit α-hemolysin production

• Published in: World journal of microbiology & biotechnology 2024-09, Vol.40 (9), p.265-265, Article 265
• Main Authors: Liu, Chang, Hou, Juan, Ren, Xinran, Guo, Xuerui, Wang, Bingmei, Song, Wu, Wang, Li, Wang, Guangshu
• Format: Article
• Language: English
• Subjects: Antibiotic resistance; Antibiotics; Applied Microbiology; Bacteria; Bacterial diseases; Biochemistry; Biomedical and Life Sciences; Biotechnology; Cell membranes; cytotoxins; dose response; Drug development; Drug resistance; Environmental Engineering/Biotechnology; genes; hemolysis; In vivo methods and tests; L-Lactate dehydrogenase; Lactate dehydrogenase; Life Sciences; Medical innovations; Methicillin; methicillin-resistant Staphylococcus aureus; mice; Microbiology; Oxacillin; Pneumonia; Quorum sensing; Staphylococcus aureus; Staphylococcus infections; therapeutics; Thermal stability; Virulence; Virulence factors
• ISSN: 0959-3993; 1573-0972; 1573-0972
• DOI: 10.1007/s11274-024-04052-5

The increasing prevalence of infections related to methicillin-resistant Staphylococcus aureus (MRSA) necessitates the exploration of innovative therapeutic strategies that diverge from conventional antibiotic treatments. This is imperative to effectively combat resistance and manage these infections. The adoption of antivirulence strategies has emerged as a particularly promising avenue. This approach applies a heightened selective pressure on pathogens, thereby diminishing the likelihood of bacteria evolving resistance to antibiotics. In our pursuit of novel therapeutics for treating MRSA infections, we have focused on agents that inhibit the virulence of S. aureus without impeding its growth, aiming to minimize the development of drug resistance. α-Hemolysin, a critical virulence factor encoded by the hla gene, is a cytotoxin that forms pores in host cell membranes and plays a pivotal role in the progression of disease during bacterial infections. Herein, we identified that norwogonin could effectively inhibit Hla production via targeting agrA C , a crucial protein in quorum sensing, resulting in dose-dependent inhibition of hemolytic activity without suppressing S. aureus growth. In vitro assays illustrated that norwogonin decreased the thermal stability of agrA C , providing evidence of interaction between norwogonin and agrA C . Meanwhile, norwogonin alleviated Hla -mediated A549 cell damage and reduced lactate dehydrogenase release. In vivo studies suggested that norwogonin treatment blocked the establishment of a mouse model of pneumonia caused by S. aureus USA300. Notably, norwogonin enhanced the antibacterial potency of oxacillin. In conclusion, norwogonin is a promising candidate for treating S. aureus infections, offering a novel alternative to traditional antibiotics by targeting virulence factors and enhancing the efficacy of existing treatments.