Department of Microbiology & Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Int J Mol Sci. 2022 Jul 4;23(13):7434. doi: 10.3390/ijms23137434.
, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this finding, this study showed that both bortezomib (BTZ) and ixazomib (IXA), anticancer drugs characterized by proteasome inhibitors, have intensive inhibitory activity against . Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of (BTZ, IC = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as . BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, -infected cells that induced a persistent infection state were selectively eliminated by BTZ treatment, whereas uninfected cells survived. These results strongly suggested the potential of boron compounds based on hydrophobic dipeptides for treating chlamydial infections, including persistent infections, which may be useful for future therapeutic use in chlamydial infectious diseases.
沙眼衣原体，一种寄生的细胞内细菌，是一种主要的人类病原体，在全球范围内导致数百万人患上沙眼、性传播感染和肺炎。以前，由疏水性二肽衍生物组成的肽模拟抑制剂表现出对衣原体生长的显著抑制作用。基于这一发现，本研究表明，蛋白酶体抑制剂类抗癌药物硼替佐米（BTZ）和伊沙佐米（IXA）均对 具有强烈的抑制活性。BTZ 和 IXA 均由疏水性二肽衍生物组成，强烈限制了 的生长（BTZ，IC=24 nM）。相比之下，其他非细胞内寄生细菌，如 ，没有观察到生长抑制作用。BTZ 和 IXA 通过电子显微镜观察到对衣原体生长具有抑菌作用。令人惊讶的是，诱导持续感染状态的 感染细胞被 BTZ 处理选择性消除，而未感染的细胞存活下来。这些结果强烈表明基于疏水性二肽的硼化合物在治疗包括持续性感染在内的衣原体感染方面具有潜力，这可能对未来治疗衣原体感染性疾病具有重要意义。
