Soontarach Rosesathorn, Voravuthikunchai Supayang Piyawan, Srimanote Potjanee, Chusri Sarunyou
Center of Antimicrobial Biomaterial Innovation-Southeast Asia, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.
Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Antibiotics (Basel). 2025 May 23;14(6):538. doi: 10.3390/antibiotics14060538.
Colistin resistance among Gram-negative nosocomial pathogens is an increasing concern. The bacteriophage-encoded lytic enzyme endolysin LysAB1245, which targets bacterial peptidoglycan, was evaluated as a potential antibacterial agent in combination with colistin as a therapeutic approach. Clinical isolates of and , along with two reference strains, were used to assess the antibacterial activity of LysAB1245 and colistin, individually and in combination. Antibacterial susceptibility was assessed by broth microdilution. Synergistic interactions were determined using checkerboard assays and confirmed by time-kill kinetics. Resistance development was assessed after several rounds of exposure to each agent, either alone or in combination. In this study, the synergistic activity of the LysAB1245/colistin combination therapy was found in some clinical isolates of and , resulting in a reduction in the MICs of both LysAB1245 and colistin. The bactericidal effects, with a significant, more than 3-log reduction in CFU/mL ( < 0.01), were observed in representative synergistic isolates within 4 h of treatment with the combination of LysAB1245 at 1/4 × MIC and colistin at 1/4 × MIC. Scanning electron microscope micrographs confirmed bacterial cell damage upon treatment with the combination. Additionally, treatment with LysAB1245 in combination with colistin had no effect on the development of bacterial resistance after multiple passages. Combining LysAB1245 with a last-resort antibiotic like polymyxins (colistin) could be used as a promising new antibacterial strategy for preventing and controlling antibiotic-resistant Gram-negative bacteria.
革兰氏阴性医院病原体中的黏菌素耐药性日益引起关注。噬菌体编码的裂解酶内溶素LysAB1245可靶向细菌肽聚糖，作为一种潜在的抗菌剂与黏菌素联合使用被评估为一种治疗方法。使用肺炎克雷伯菌和大肠埃希菌的临床分离株以及两个参考菌株来单独和联合评估LysAB1245和黏菌素的抗菌活性。通过肉汤微量稀释法评估抗菌敏感性。使用棋盘法确定协同相互作用，并通过时间杀菌动力学进行确认。在单独或联合接触每种药物几轮后评估耐药性的产生。在本研究中，LysAB1245/黏菌素联合治疗在一些肺炎克雷伯菌和大肠埃希菌的临床分离株中发现了协同活性，导致LysAB1245和黏菌素的最低抑菌浓度均降低。在用1/4×最低抑菌浓度的LysAB1245和1/4×最低抑菌浓度的黏菌素联合治疗4小时内，在代表性的协同分离株中观察到杀菌效果，CFU/mL显著降低超过3个对数（P<0.01）。扫描电子显微镜照片证实联合治疗后细菌细胞受损。此外，LysAB1245与黏菌素联合治疗对多次传代后的细菌耐药性发展没有影响。将LysAB1245与多粘菌素（黏菌素）等最后手段抗生素联合使用可作为一种有前景的新抗菌策略，用于预防和控制耐抗生素革兰氏阴性菌。
