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一种新型的 thiopeptide 在体外和体外表现出协同作用的抗菌活性与对抗 Mycobacterium avium 复杂感染的 macrolide

Jiyun Park¹, Lee-Han Kim¹, Ju Mi Lee¹

¹Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Institute for Immunology and Immunological Disease, Seoul 03722, South Korea.

ACS infectious diseases

|December 16, 2025

概括

AJ-099是一种新型硫抗生素,对Mycobacterium avium复合体 (MAC) 肺部感染表现出强烈的活性. 它与克拉里胺素协同作用,为药物敏感性和耐药性MAC感染提供了有希望的治疗方法.

科学领域:

微生物学微生物学
药理学药理学是指药理学的学科.
传染性疾病传染性疾病

背景情况:

目前用于治疗由Mycobacterium avium复合体 (MAC) 引起的肺部疾病的疗法存在局限性.
硫类抗生素显示出抗菌效果的前景,但其溶解性不佳.
迫切需要新型药物来对抗MAC感染,特别是抗宏化物耐药菌株.

研究的目的:

开发和评估AJ-099,一种具有改善溶解度和增强抗菌功能的硫衍生物,对MAC有增强的抗菌作用.
评估AJ-099的体外和体内疗效,单独使用或与清红素 (CLR) 结合使用.

主要方法:

AJ-099是作为一种 thiopeptide 衍生物开发出来的.
试验室抗菌活性与临床MAC分离物 (对宏素敏感和耐药) 进行了测试.
活体疗效在小鼠模型中进行了评估,将AJ-099加CLR与标准治疗进行了比较.

主要成果:

AJ-099在体外对MAC分离物 (MIC ≤0.125-0.5μg/mL) 显示出强烈的活性.
AJ-099显示了巨细胞内MAC的显著增长抑制.
AJ-099与CLR表现出协同作用,减少细胞内MAC负担并改善体内细菌清除.
组合疗法在减少细菌负载和肺炎方面表现优于标准治疗.

结论:

AJ-099是治疗肺部MAC感染的有希望的候选者,特别是与宏化物结合使用时.
它对抗抗宏类耐药MAC菌株的强有力的活性表明可能存在耐火性感染.

关键词:

这种复杂的菌株是Mycobacterium avium.它们具有抗菌细菌活性.在体内疗效 in vivo疗效抗化物耐药的Mycobacterium avium复合体是一种复合体.有协同效应的效应.铁类药物铁类药物铁类药物

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