Pan Yandi, Liu Hongdou, Liu Yuqian, Zhang Tingting, Xu Shichao, Lu Yilin, Lu Yi, Xu Liuyi, Hu Xiaoxiang, Cao Xuefeng, Fang Rendong, Peng Lianci
Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.
Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.
Int Immunopharmacol. 2025 Aug 28;161:115053. doi: 10.1016/j.intimp.2025.115053. Epub 2025 Jun 16.
With the increasing emergence of antimicrobial resistance, the rise of multidrug-resistant Streptococcus suis (S. suis) has caused a great threat on global public health. The combination of antimicrobial peptide (AMP) and antibiotics is an efficient strategy to enhance antibacterial efficacy and combat bacterial antibiotic resistance. In this study, the antibacterial efficacy of chicken-derived AMP CATH-1 combined with tetracycline against S. suis infection was investigated in vitro and in vivo. The results showed that combination of CATH-1 and tetracycline exerted effectively anti-S. suis activity, which rapidly killed all tested bacteria in 60 min. In the mice infection model, CATH-1 combined with tetracycline improved survival rate of SC19-infected mice, reduced bacterial load in different tissues and alleviated the inflammatory response as well as inflammatory damage. Furthermore, CATH-1 reduced the emergence of bacterial resistance to tetracycline. Mechanically, CATH-1 disrupted cell membrane via SEM observation and SYTO9/PI staining. CATH-1 in combination with tetracycline aggravated reactive oxygen species (ROS) accumulation and proton motive force (PMF) disruption compared to CATH-1 or tetracycline alone. In addition, CATH-1 inhibited efflux pump function. Importantly, we identified a critical gene steAB associated with biofilm formation and CATH-1 alone or in combination with tetracycline inhibited biofilm formation. Our study shows effective anti-S. suis infection of CATH-1-tetracycline synergy, which provides the basis on the development of AMP as additives to antibiotics.
随着抗菌药物耐药性的日益出现，多重耐药性猪链球菌（S. suis）的出现对全球公共卫生造成了巨大威胁。抗菌肽（AMP）与抗生素联合使用是提高抗菌效果和对抗细菌抗生素耐药性的有效策略。在本研究中，对鸡源AMP CATH-1与四环素联合使用对猪链球菌感染的体外和体内抗菌效果进行了研究。结果表明，CATH-1与四环素联合使用能有效发挥抗猪链球菌活性，在60分钟内迅速杀灭所有测试细菌。在小鼠感染模型中，CATH-1与四环素联合使用提高了SC19感染小鼠的存活率，降低了不同组织中的细菌载量，减轻了炎症反应以及炎症损伤。此外，CATH-1降低了细菌对四环素耐药性的出现。从机制上讲，通过扫描电子显微镜观察和SYTO9/PI染色发现CATH-1破坏了细胞膜。与单独使用CATH-1或四环素相比，CATH-1与四环素联合使用加剧了活性氧（ROS）积累和质子动力势（PMF）破坏。此外，CATH-1抑制了外排泵功能。重要的是，我们鉴定出一个与生物膜形成相关的关键基因steAB，CATH-1单独或与四环素联合使用均能抑制生物膜形成。我们的研究表明CATH-1 - 四环素协同作用对猪链球菌感染具有有效的抗菌作用，这为将AMP开发为抗生素添加剂提供了依据。
