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Published on: August 11, 2012
An in vitro model of azithromycin-induced persistent Chlamydia trachomatis infection
Yaohua Xue1,2, Heping Zheng2, Zhida Mai2
1Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China.
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.
Insights
This study developed an in vitro model for azithromycin-resistant Chlamydia trachomatis infections. The model shows bacteria persist and recover after antibiotic removal, aiding new treatment development.
Area of Science:
- Microbiology
- Cell Biology
- Antimicrobial Resistance
Background:
- Single-dose azithromycin is the standard treatment for Chlamydia trachomatis.
- Understanding treatment failure mechanisms is crucial for combating persistent infections.
Purpose of the Study:
- To establish a novel in vitro cell model simulating azithromycin-induced persistent Chlamydia trachomatis infection.
- To investigate the characteristics and recovery patterns of persistent C. trachomatis.
- To identify potential molecular mechanisms underlying azithromycin persistence.
Main Methods:
- Development of an in vitro cell culture model for persistent infection.
- Dose-time-dependent inhibition assays.
- Transmission electron microscopy (TEM) for ultrastructural analysis.
- Reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR) for gene expression analysis.
Main Results:
- Azithromycin inhibited C. trachomatis replication in a dose-time-dependent manner.
- Electron microscopy revealed enlarged, aberrant, non-infectious reticulate bodies in persistent inclusions.
- C. trachomatis demonstrated recovery within 24 hours after azithromycin removal.
- No mutations in 23S rRNA, L4, or L22 genes were observed in persistent infections.
- Upregulation of euo and downregulation of omcB gene expression were noted in azithromycin-treated infections.
Conclusions:
- The established in vitro model effectively mimics azithromycin-induced persistent C. trachomatis infection.
- Persistent C. trachomatis retains viability and recovery potential after antibiotic withdrawal.
- The study provides insights into the molecular basis of persistence, guiding the development of novel therapeutic strategies against C. trachomatis.
