Chlamydia spp. development is differentially altered by treatment with the LpxC inhibitor LPC-011.
Chlamydia spp. development is differentially altered by treatment with the LpxC inhibitor LPC-011.
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DOI：
10.1186/s12866-017-0992-8
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发表时间：
2017-04-24
期刊：
影响因子：
4.2
通讯作者：
Dolan BP
中科院分区：
文献类型：
--
作者：
Cram ED;Rockey DD;Dolan BP
衣原体是一种专性细胞内细菌，可感染广泛的哺乳动物宿主。相关属的成员是各种脊椎动物和无脊椎动物的病原体。尽管衣原体具有多样性，但所有物种都含有一个外膜脂寡糖(LOS)，它由一个属保守、属定义的三糖3-脱氧-D-甘露-OCT-2-磺酸Kdo区组成。最近对脂多糖抑制剂的研究表明，LOS在沙眼衣原体的发育周期中是重要的，在Rb和EB分化过程中。在这里，我们探索其中一种抑制物，LPC-011，对五种衣原体的发育周期的影响。对药物的敏感性在一些物种中有所不同，而在另一些物种之间则是保守的。我们观察到，在一些衣原体物种中，抑制LOS的生物合成会导致异常网状小体的形成，而在其他物种中，网状小体没有观察到变化。然而，LOS产量的损失阻碍了所有被测试物种的衣原体繁殖周期的完成。在以前的研究中，我们发现沙眼衣原体和豚鼠衣原体感染增强了模型自肽的MHC-I类抗原呈递。我们发现，用LPC-011治疗可以防止所有被测试的衣原体感染引起的宿主多肽呈现增强。这些数据表明，LOS合成是产生感染性后代所必需的，抑制LOS合成会导致某些衣原体物种的变异，这对使用LOS合成抑制剂作为潜在的抗生素具有重要意义。
Chlamydia species are obligate intracellular bacteria that infect a broad range of mammalian hosts. Members of related genera are pathogens of a variety of vertebrate and invertebrate species. Despite the diversity of Chlamydia, all species contain an outer membrane lipooligosaccharide (LOS) that is comprised of a genus-conserved, and genus-defining, trisaccharide 3-deoxy-D-manno-oct-2-ulosonic acid Kdo region. Recent studies with lipopolysaccharide inhibitors demonstrate that LOS is important for the C. trachomatis developmental cycle during RB- > EB differentiation. Here, we explore the effects of one of these inhibitors, LPC-011, on the developmental cycle of five chlamydial species. Sensitivity to the drug varied in some of the species and was conserved between others. We observed that inhibition of LOS biosynthesis in some chlamydial species induced formation of aberrant reticulate bodies, while in other species, no change was observed to the reticulate body. However, loss of LOS production prevented completion of the chlamydial reproductive cycle in all species tested. In previous studies we found that C. trachomatis and C. caviae infection enhances MHC class I antigen presentation of a model self-peptide. We find that treatment with LPC-011 prevents enhanced host-peptide presentation induced by infection with all chlamydial-species tested. The data demonstrate that LOS synthesis is necessary for production of infectious progeny and inhibition of LOS synthesis induces aberrancy in certain chlamydial species, which has important implications for the use of LOS synthesis inhibitors as potential antibiotics.