Bortezomib Eliminates Persistent Chlamydia trachomatis Infection through Rapid and Specific Host Cell Apoptosis.
Ryota ItohYusuke KuriharaMichinobu YoshimuraKenji HiromatsuPublished in: International journal of molecular sciences (2022)
Chlamydia trachomatis , 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 Chlamydia . Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of Chlamydia (BTZ, IC 50 = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as Escherichia coli . BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, Chlamydia -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.
Keyphrases
- induced apoptosis
- escherichia coli
- infectious diseases
- endothelial cells
- electron microscopy
- ionic liquid
- cell proliferation
- multiple myeloma
- magnetic resonance
- hiv infected
- signaling pathway
- risk assessment
- newly diagnosed
- endoplasmic reticulum stress
- oxidative stress
- high glucose
- cell death
- current status
- human health
- klebsiella pneumoniae
- respiratory failure
- diabetic rats
- water soluble