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The Genital Tract Virulence Factor pGP3 Is Essential for Chlamydia muridarum Colonization in the Gastrointestinal
Lili Shao1,2, Tianyuan Zhang1,3, Jose Melero1
1Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Abstract:
The cryptic plasmid is essential for Chlamydia muridarum dissemination from the genital tract to the gastrointestinal (GI) tract. Following intravaginal inoculation, a C. muridarum strain deficient in plasmid-encoded pGP3 or pGP4 but not pGP5, pGP7, or pGP8 failed to spread to the mouse gastrointestinal tract, although mice infected with these strains developed productive genital tract infections. pGP3- or pGP4-deficient strains also failed to colonize the gastrointestinal tract when delivered intragastrically. pGP4 regulates pGP3, while pGP3 does not affect pGP4 expression, indicating that pGP3 is critical for C. muridarum colonization of the gastrointestinal tract. Mutants deficient in GlgA, a chromosome-encoded protein regulated by pGP4, also consistently colonized the mouse gastrointestinal tract. Interestingly, C. muridarum colonization of the gastrointestinal tract positively correlated with pathogenicity in the upper genital tract. pGP3-deficient C. muridarum strains did not induce hydrosalpinx or spread to the GI tract even when delivered to the oviduct by intrabursal inoculation. Thus, the current study not only has revealed that pGP3 is a novel chlamydial colonization factor in the gastrointestinal tract but also has laid a foundation for investigating the significance of gastrointestinal Chlamydia.
Insights
The cryptic plasmid
Area of Science:
- Microbiology
- Infectious Diseases
- Molecular Biology
Background:
- Chlamydia muridarum utilizes a cryptic plasmid for dissemination.
- Understanding plasmid roles is crucial for controlling chlamydial infections.
Purpose of the Study:
- To investigate the role of cryptic plasmid genes in Chlamydia muridarum dissemination.
- To identify specific plasmid factors essential for gastrointestinal tract colonization.
Main Methods:
- Generating and testing Chlamydia muridarum strains deficient in specific plasmid genes (pGP3, pGP4, pGP5, pGP7, pGP8).
- Assessing bacterial spread from the genital to the gastrointestinal tract in a mouse model.
- Evaluating colonization ability following intragastric inoculation.
- Analyzing the regulation between pGP3 and pGP4.
- Investigating the role of GlgA, a chromosome-encoded protein.
Main Results:
- Plasmid-encoded pGP3 and pGP4 are essential for Chlamydia muridarum dissemination to the mouse gastrointestinal tract.
- pGP3 is critical for gastrointestinal colonization, with pGP4 regulating pGP3 expression.
- GlgA-deficient mutants also failed to colonize the gastrointestinal tract.
- Gastrointestinal colonization correlated with upper genital tract pathogenicity.
Conclusions:
- pGP3 is a novel chlamydial colonization factor for the gastrointestinal tract.
- The cryptic plasmid plays a significant role in Chlamydia muridarum's ability to colonize the GI tract.
- This study provides a foundation for further research into gastrointestinal Chlamydia infections.