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Published on: June 10, 2020
Characterization and comparison of differentially expressed genes involved in Chlamydia psittaci persistent infection
Yuqing Chen1, Chuan Wang2, Jing Mi3
1Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan, 421001, China; Clinical Microbiology Laboratory, Xiangtan Central Hospital, Xiangtan, 411100, China.
Abstract:
Chlamydia psittaci is an obligate intracellular zoonotic pathogen that can enter a persistence state in host cells. While the exact pathogenesis is not well understood, this persistence state may play an important role in chronic Chlamydia disease. Here, we assess the effects of chlamydial persistence state in vitro and in vivo by transmission electron microscopy (TEM) and cDNA microarray assays. First, IFN-γ-induced C. psittaci persistence in HeLa cells resulted in the upregulation of 68 genes. These genes are involved in protein translation, carbohydrate metabolism, nucleotide metabolism, lipid metabolism and general stress. However, 109 genes were downregulated following persistent C. psittaci infection, many of which are involved in the TCA cycle, expression regulation and transcription, protein secretion, proteolysis and transport, membrane protein, presumed virulence factor, cell division and late expression. To further study differential gene expression of C. psittaci persistence in vivo, we established an experimentally tractable mouse model of C. psittaci persistence. The C. psittaci-infected mice were gavaged with either water or amoxicillin (amox), and the results indicated that the 20 mg/kg amox-exposed C. psittaci were viable but not infectious. Differentially expressed genes (DEGs) screened by cDNA microarray were detected, and interestingly, the results showed upregulation of three genes (euo, ahpC, prmC) and downregulation of five genes (pbp3, sucB_1, oppA_4, pmpH, ligA) in 20 mg/kg amox-exposed C. psittaci, which suggests that antibiotic treatment in vivo can induce chlamydial persistence state and lead to differential gene expression. However, the discrepancy on inducers between the two models requires more research to supplement. The results may help researchers better understand survival advantages during persistent infection and mechanisms influencing C. psittaci pathogenesis or evasion of the adaptive immune response.
Insights
Chlamydia psittaci persistence alters gene expression in host cells and mice. Antibiotic treatment in vivo induces a viable but non-infectious state, impacting chlamydial gene expression and survival mechanisms.
Area of Science:
- Microbiology
- Pathogen Biology
- Host-Pathogen Interactions
Background:
- Chlamydia psittaci is a zoonotic pathogen capable of entering a persistence state within host cells.
- The precise mechanisms of Chlamydia psittaci pathogenesis and the role of persistence in chronic disease remain incompletely understood.
Purpose of the Study:
- To investigate the molecular effects of Chlamydia psittaci persistence in vitro and in vivo.
- To identify differentially expressed genes associated with Chlamydia psittaci persistence induced by IFN-γ and amoxicillin.
Main Methods:
- In vitro studies utilized HeLa cells with IFN-γ-induced Chlamydia psittaci persistence, analyzed via cDNA microarray.
- An in vivo mouse model was established to study Chlamydia psittaci persistence, with mice treated with amoxicillin and analyzed using cDNA microarray.
Main Results:
- In vitro, Chlamydia psittaci persistence led to the upregulation of 68 genes (e.g., protein translation, metabolism) and downregulation of 109 genes (e.g., TCA cycle, virulence factors).
- In vivo, amoxicillin treatment resulted in viable but non-infectious Chlamydia psittaci, with specific gene upregulation (euo, ahpC, prmC) and downregulation (pbp3, sucB_1, oppA_4, pmpH, ligA).
Conclusions:
- Chlamydial persistence significantly alters gene expression profiles both in vitro and in vivo.
- Antibiotic treatment can induce a persistent, non-infectious state in Chlamydia psittaci, affecting its gene expression and potentially its survival and immune evasion strategies.
