PDF(Pubmed)
Abstract：
It is crucial to discover novel antimicrobial drugs to combat resistance. This study investigated the antibacterial properties of halicin (SU3327), an AI-identified anti-diabetic drug, against 13 kinds of common clinical pathogens of animal origin, including multidrug-resistant strains. Employing minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assessments, halicin demonstrated a broad-spectrum antibacterial effect. Time-killing assays revealed its concentration-dependent bactericidal activity against Escherichia coli ATCC 25922 (E. coli ATCC 25922), Staphylococcus aureus ATCC 29213 (S. aureus ATCC 29213), and Actinobacillus pleuropneumoniae S6 (APP S6) after 4 h of treatment at concentrations above the MIC. Halicin exhibited longer post-antibiotic effects (PAEs) and sub-MIC effects (PA-SMEs) for E. coli 25922, S. aureus 29213, and APP S6 compared to ceftiofur and ciprofloxacin, the commonly used veterinary antimicrobial agents, indicating sustained antibacterial action. Additionally, the results of consecutive passaging experiments over 40 d at sub-inhibitory concentrations showed that bacteria exhibited difficulty in developing resistance to halicin. Toxicology studies confirmed that halicin exhibited low acute toxicity, being non-mutagenic, non-reproductive-toxic, and non-genotoxic. Blood biochemical results suggested that halicin has no significant impact on hematological parameters, liver function, and kidney function. Furthermore, halicin effectively treated respiratory A. pleuropneumoniae infections in murine models. These results underscore the potential of halicin as a new antibacterial agent with applications against clinically relevant pathogens in veterinary medicine.
摘要：
发现新型抗菌药物对对抗耐药性至关重要。这项研究调查了卤素（SU3327）的抗菌性能，一种人工智能识别的抗糖尿病药物，针对13种常见的动物源性临床病原体，包括多重耐药菌株。采用最低抑菌浓度（MIC）和最低杀菌浓度（MBC）评估，卤素具有广谱抗菌作用。时间杀灭试验显示其对大肠杆菌ATCC25922的浓度依赖性杀菌活性（E。大肠杆菌ATCC25922），金黄色葡萄球菌ATCC29213(S.金黄色葡萄球菌ATCC29213），和以高于MIC的浓度处理4小时后的胸膜肺炎放线杆菌S6（APPS6）。与头孢噻呋和环丙沙星相比，Halicin对大肠杆菌25922，金黄色葡萄球菌29213和APPS6表现出更长的抗生素后效应（PAEs）和亚MIC效应（PA-SME）。常用的兽用抗菌剂，表明持续的抗菌作用。此外,在亚抑制浓度下连续传代实验超过40d的结果表明，细菌对卤素的抗性难以发展。毒理学研究证实，卤素表现出低急性毒性，是非诱变的，非生殖毒性，和非遗传毒性。血液生化结果提示卤素对血液学参数无显著影响,肝功能,和肾功能。此外，卤素有效治疗小鼠模型中的呼吸道肺炎A.这些结果强调了卤素作为新的抗菌剂的潜力，可在兽医学中应用于临床相关病原体。
