An in vitro model of azithromycin-induced persistent Chlamydia trachomatis infection

Abstract

Single-dose azithromycin is recommended for treating Chlamydia trachomatis infections. Here, we established an in vitro cell model of azithromycin-induced persistent infection. Azithromycin inhibited the replication of C. trachomatis in a dose-time-dependent manner. Electron microscopy indicated that small inclusions in the induced model contained enlarged, aberrant and non-infectious reticulate bodies. RT-PCR showed that C. trachomatis still has the ability to express the unprocessed 16S rRNA gene in the model and that C. trachomatis recovered after the removal of azithromycin with a peak recovery time of 24 h. The mutations in 23S rRNA, L4 and L22 genes were not found in persistent infection, and qRT-PCR analysis showed that the relative expression level of euo in azithromycin treated infection was upregulated while omcB was downregulated. In summary, this study provides a novel in vitro cell model to examine the characteristics of azithromycin-induced persistent infection and contribute to the development of treatments for C. trachomatis infection.

Evaluating the Antibiotic Susceptibility of Chlamydia – New Approaches for in Vitro Assays

“…Moreover, heterotypic resistance in various Chlamydia species has been observed upon survival of a small proportion of bacteria exposed to antibiotic concentrations well above the minimal inhibitory concentration (MIC) and might be a cause of treatment failure in patients, a phenomenon also referred to as drug indifference, tolerance, or persistence ( Suchland et al, 2003 ; Sandoz and Rockey, 2010 ). In Chlamydia , persistence, or the chlamydial stress response, is known to occur specifically upon exposure to antibiotics affecting cell wall synthesis, such as penicillin ( Lewis, 2007 ; Sandoz and Rockey, 2010 ; Schoborg, 2011 ; Borel et al, 2014 ; Zheng et al, 2015 ; Leonard et al, 2017 ; Xue et al, 2017 ).…”

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

“…In this study, we demonstrated that the RSK inhibitors LJH685 and LJI308 reduced Chlamydia infection in three cell lines, while siRNA-mediated RSK knockdown inhibited Chlamydia negative for mycoplasma infection as determined by a detection kit according to the manufacturer's recommendations (Bioind, Tel Aviv, Israel). Chlamydia was propagated as previously described (Xue et al, 2017).…”

Transcriptional Landscape of Waddlia chondrophila Aberrant Bodies Induced by Iron Starvation

“…Besides euo, the late gene omcB, encoding the outer membrane complex protein B, is also considered as a molecular marker of persistence. omcB is down-regulated in persistent Chlamydia induced either by iron deprivation, interferon-γ or azithromycin [33,63,[72][73][74]. In contrast, OmcB protein levels were unaffected in iron-starved C. pneumoniae [75].…”