Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force

作者：Bingqian Xue, Xiaojun Liu, Shuji Gao, Yingying Quan, Yuxin Wang, Yuxin Wang, Li Yi, Yang Wang, Yang Wang · 发表于：BMC Veterinary Research · 年份：2025 · DOI：10.1186/s12917-024-04430-z · 被引用次数：6 · 研究领域：Andrographolide Research and Applications、Streptococcal Infections and Treatments、Inflammasome and immune disorders

BACKGROUND: The global rise in multidrug-resistant bacteria has significantly undermined the efficacy of traditional antibiotics. Multidrug-resistant Streptococcus suis (S. suis), a pathogen capable of infecting pigs and humans, has been identified as a critical threat, causing severe meningitis and rapid mortality. In response, researchers have increasingly focused on herbal compounds as non-traditional antimicrobial agents, which can inhibit bacterial growth while minimizing the risk of resistance development. This study investigates the mechanism through which andrographolide (AP) restores the susceptibility of S. suis to aminoglycoside antibiotics. METHODS: The intracellular ΔpH in S. suis was assessed using the 2',7' -bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCCF-AM) probe to evaluate alterations in the proton motive force (PMF) following treatment with AP. Non-targeted metabolomics was employed to confirm changes in the metabolic profile of S. suis upon exposure to AP. Finally, an in vivo infection model was utilized to evaluate the therapeutic efficacy of AP in combination with antibiotics. RESULTS: Extensive in vitro experiments demonstrated that AP significantly enhances the activity of aminoglycoside antibiotics against diverse pathogens, including S. suis. Further studies revealed that bacterial death results from AP-mediated upregulation of the S. suis PMF, which enhances cellular uptake of tobramycin (TOB). Moreover, AP significantly upregulated pyruvat...