Inhibition of the Extracellular Signal–Regulated Kinase/Ribosomal S6 Kinase Cascade Limits Chlamydia trachomatis Infection

Abstract

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Rhein inhibits Chlamydia trachomatis infection by regulating pathogen-host cell

“…The influence-on-post-adsorption assay showed a significant inhibitory effect of rhein ( Figures 4B–D ). Our previous study demonstrated that the extracellular signaling-regulated kinase (ERK)/ribosomal S6 kinase (RSK) signaling pathway was important in C. trachomatis infection ( 46 ). To investigate the mechanism of action of rhein in C. trachomatis infection, the protein of ERK and RSK were performed by western blotting in the current study on C. trachomatis -infected cells treated with rhein for different times post-infection.…”

“…Rhein was previously reported to have effective antibacterial and antiviral activity against S. aureus, Helicobacter pylori , influenza A virus, and hepatitis B virus (HBV) ( 33 , 36 , 46 ). The mechanism of action of rhein was shown to involve direct impairment of pathogens or regulation of host cell signaling pathways.…”

“…ERK signaling pathways are the most prominent kinase signaling network utilized by C. trachomatis and have been characterized as being instrumental in nutrient acquisition, host cell apoptosis resistance, immune responses, and even pathology associated with chlamydial infections ( 56 – 58 ). Moreover, our previous study suggested that ERK/RSK may be a novel target for C. trachomatis therapeutics ( 46 ). In this study, phosphorylated ERK/RSK was reduced upon exposure to rhein, suggesting that rhein may inhibit C. trachomatis infection by regulating the ERK/RSK pathway.…”

Akt Phosphorylation Influences Persistent Chlamydial Infection and Chlamydia-Induced Golgi Fragmentation Without Involving Rab14

“…Therefore, Akt appears to be a more valuable upstream therapeutic target than Rab14 in persistent chlamydial infection. A recent study has demonstrated that several inhibitors of the ERK/RSK pathway represent potential treatment options for Host-directed therapy (HDT), limiting the development of Chlamydia ( Xue et al., 2020 ). Our study suggests that Akt inhibitors could also be a member of HDT, and help treat both acute and persistent chlamydial infection.…”

Recent Advances in Treatment of Recurrent Spontaneous Abortion

“…However, further clinical studies are needed to determine the development of drug resistance and potential protective effects of gepotidacin in combination with doxycycline. 46 SiRNA knockout showed that Erk12 and RSK1 were important pathways for Chlamydia infection, and the first-class Erk12 inhibitor BVD-523, currently undergoing phase II clinical trials, inhibited Chlamydia infection in both cell cultures and mouse models; in other words, kinases in the Erk, RSK pathway may act as host-directed therapy CT. 47 A study 48 pointed out that systemic enzyme therapy can reduce the T H 2 cells, thus reducing the imbalance of local inflammatory processes and the formation of immune disorders, improving the effectiveness of antibiotic therapy and reducing the occurrence of adverse effects. The results showed that the clinical and microbiological response rates in CT infection patients were 97.6% > 78.6% with doxycycline and root enzyme combination therapy, compared with monotherapy (doxycycline), which were statistically significant (OR, 11.2; 95% CI, 1.3–247.9; P = 0.007).…”