关键词: Chlamydia trachomatis Neisseria gonorrhea antibacterial compound screen mouse model pre-exposure prophylaxis prevention sexually transmitted infections

Mesh : Animals Chlamydia trachomatis / drug effects Chlamydia Infections / drug therapy microbiology prevention & control Pentamidine / pharmacology Disease Models, Animal Mice Humans Anti-Bacterial Agents / pharmacology Female Drug Evaluation, Preclinical Gonorrhea / drug therapy microbiology Neisseria gonorrhoeae / drug effects HeLa Cells

来  源:   DOI:10.1016/j.xcrm.2024.101643   PDF(Pubmed)

Abstract:
Chlamydia trachomatis (Ct) is the most common cause for bacterial sexually transmitted infections (STIs) worldwide with a tremendous impact on public health. With the aim to unravel novel targets of the chlamydia life cycle, we screen a compound library and identify 28 agents to significantly reduce Ct growth. The known anti-infective agent pentamidine-one of the top candidates of the screen-shows anti-chlamydia activity in low concentrations by changing the metabolism of host cells impairing chlamydia growth. Furthermore, it effectively decreases the Ct burden upon local or systemic application in mice. Pentamidine also inhibits the growth of Neisseria gonorrhea (Ng), which is a common co-infection of Ct. The conducted compound screen is powerful in exploring antimicrobial compounds against Ct in a medium-throughput format. Following thorough in vitro and in vivo assessments, pentamidine emerges as a promising agent for topical prophylaxis or treatment against Ct and possibly other bacterial STIs.
摘要:
沙眼衣原体(Ct)是全球细菌性性传播感染(STIs)的最常见原因,对公共卫生产生巨大影响。为了解开衣原体生命周期的新目标,我们筛选了一个化合物库,并鉴定了28种显著降低Ct生长的药物。已知的抗感染剂喷他脒-屏幕的最佳候选之一-通过改变损害衣原体生长的宿主细胞的代谢而在低浓度下显示出抗衣原体活性。此外,它有效地降低小鼠局部或全身应用时的Ct负担。Pentamidine还抑制淋病奈瑟菌(Ng)的生长,这是一种常见的CT共感染。所进行的化合物筛选在以中等通量形式探索抗Ct的抗微生物化合物方面是强大的。经过全面的体外和体内评估,喷脒是一种有前途的药物,用于局部预防或治疗Ct和其他细菌性传播感染。
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