Benzylidene Acylhydrazides Inhibit Chlamydial Growth in a Type III Secretion- and Iron Chelation-Independent Manner
Benzylidene Acylhydrazides Inhibit Chlamydial Growth in a Type III Secretion- and Iron Chelation-Independent Manner
复制标题
苯亚甲基酰肼以不依赖于 III 型分泌和铁螯合的方式抑制衣原体生长
DOI：
10.1128/jb.01677-14
复制
发表时间：
2014-08-01
影响因子：
3.2
通讯作者：
Fan, Huizhou
中科院分区：
文献类型：
--
作者：
Bao, Xiaofeng;Gylfe, Asa;Fan, Huizhou
衣原体是人类和动物的广泛的革兰氏阴性病原体。水杨醛酰肼，作为耶尔森氏菌属中III型分泌系统（T3 SS）的抑制剂开发，对衣原体感染有抑制作用。然而，这些抑制剂也具有螯合铁的能力，它们的抗衣原体作用可能是由铁饥饿引起的。因此，我们探索了水杨醛酰肼的修饰，目的是将抗衣原体作用与铁饥饿解偶联。我们发现，苄叉酰肼，不能螯合铁，抑制衣原体的生长。生化和遗传分析表明，衍生物化合物通过T3 SS-独立的机制抑制衣原体。四个单核苷酸多态性被确定在一个衣原体muridarum变种耐苄叉酰肼，但它可能是必要的分离的突变，以区分其在耐药表型的作用。亚苄基酰肼被宿主细胞和益生菌阴道乳杆菌物种良好耐受，因此具有潜在的治疗价值。
Chlamydiae are widespread Gram-negative pathogens of humans and animals. Salicylidene acylhydrazides, developed as inhibitors of type III secretion system (T3SS) in Yersinia spp., have an inhibitory effect on chlamydial infection. However, these inhibitors also have the capacity to chelate iron, and it is possible that their antichlamydial effects are caused by iron starvation. Therefore, we have explored the modification of salicylidene acylhydrazides with the goal to uncouple the antichlamydial effect from iron starvation. We discovered that benzylidene acylhydrazides, which cannot chelate iron, inhibit chlamydial growth. Biochemical and genetic analyses suggest that the derivative compounds inhibit chlamydiae through a T3SS-independent mechanism. Four single nucleotide polymorphisms were identified in a Chlamydia muridarum variant resistant to benzylidene acylhydrazides, but it may be necessary to segregate the mutations to differentiate their roles in the resistance phenotype. Benzylidene acylhydrazides are well tolerated by host cells and probiotic vaginal Lactobacillus species and are therefore of potential therapeutic value.