Bortezomib exhibited bacteriostatic activity and pro-inflammatory effect against Mycoplasma pneumoniae

Mycoplasma pneumoniae (MP) is an important respiratory pathogen. Growth inhibition and regulation of inflammation in lung are key to the treatment of MP infections. Bortezomib, a proteinase inhibitor, was found to possess both functions in this study. Firstly, bortezomib showed dose-dependent bacteriostatic activity against MP in culture medium. Decreases in glucose catabolism (changes of pH) and colony-forming units (CFUs) were detected at 3 d post-incubation (bortezomib>10 nM). The MP cells incubated with bortezomib of 25 nM exhibited decreases in contents of protein and carbohydrate comparing to normal MP cells. When co-incubated with lung epithelial cells, reductions in MP CFUs and viability of lung epithelial cells were detected. Transcriptome analysis revealed that bortezomib (25 nM) influence the protein digestion and absorption pathways in A549 cells. Meanwhile, bortezomib up-regulated the PI3K-Akt and JAK-STAT pathways and down-regulated the MAPK pathway in MP-infected cells. Western-blot detection revealed that bortezomib reduce the increase in TLR4 triggered by MP, and reduce the level of IκBα. Meanwhile, higher level of extracellular IL-6 was detected in MP-infected cells post bortezomib treatment. In addition, the secretions of bortezomib-treated A549 cells showed promoting effects on M1-polarization of macrophages. In Balb/c mice, oral administration of bortezomib promoted the production of MP-specific antibodies and reduced pulmonary damage at 7th day post infection. In conclusion, bortezomib exerts a direct bacteriostatic effect on MP in vitro, it also plays roles in the regulation of inflammatory pathways during MP infection.