Bortezomib Eliminates Persistent Chlamydia trachomatis Infection through Rapid and Specific Host Cell Apoptosis

Int J Mol Sci. 2022 Jul 4;23(13):7434. doi: 10.3390/ijms23137434.


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, IC50 = 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.

Keywords: Chlamydia infection; anticancer drug; bortezomib; persistent infection.

MeSH terms

  • Apoptosis
  • Bortezomib / pharmacology
  • Chlamydia Infections* / drug therapy
  • Chlamydia Infections* / microbiology
  • Chlamydia trachomatis*
  • Dipeptides / pharmacology
  • Humans


  • Dipeptides
  • Bortezomib

Grants and funding

This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science: 19K16659 (Y.K.), JP21K16329 (M.Y.).