Chlamydia trachomatis virulence factor CT135 is stable in vivo but highly polymorphic in vitro
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Updated: Apr 8, 2026
Forward Genetic Approaches in Chlamydia trachomatis
Published on: October 23, 2013
Christine Bonner1, Harlan D Caldwell2, John H Carlson2
1National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB R3E 3R2, Canada.
Abstract:
Chlamydia trachomatis is an important human pathogen causing both ocular and sexually transmitted disease. Recently, we identified CT135 as an important virulence determinant in a mouse infection model. Results from CEL 1 digestion assays and sequencing analyses indicated that CT135 was much more polymorphic in high in vitro passage reference serovars than it was in clinical strains that had undergone limited passaging. Herein, we used targeted next-generation sequencing of the CT134-135 locus, from reference strains and clinical isolates, enabling accurate discovery of single nucleotide polymorphisms and other population genetic variations. Our results indicate that CT134 is stable in all C. trachomatis serovars examined. In contrast, CT135 is highly polymorphic in high-passaged reference ocular and non-LGV genital serovars, with the majority of the mutations resulting in gene disruption. In low-passaged ocular clinical isolates, CT135 was frequently disrupted, whereas in genital clinical isolates CT135 was intact in almost all instances. When a serovar K isolate, with an intact CT134 and CT135, was subjected to serial passage in vitro CT134 remained invariable, while numerous gene interrupting mutations rapidly accumulated in CT135. Collectively, our data indicate that, for genital serovars, CT135 is under strong positive selection in vivo, and negative selection in vitro.
Insights
Chlamydia trachomatis CT135 exhibits significant genetic variation, particularly in ocular and genital serovars. This gene is frequently disrupted in vitro but stable in vivo, suggesting differential selection pressures.
Area of Science:
- Microbiology
- Genetics
- Pathogen Biology
Background:
- Chlamydia trachomatis is a significant human pathogen responsible for ocular and sexually transmitted infections.
- The CT135 gene has been identified as a crucial virulence factor in C. trachomatis mouse infection models.
- Previous studies indicated CT135 exhibits higher polymorphism in high-passage reference strains compared to low-passage clinical isolates.
Purpose of the Study:
- To investigate the population genetic variations within the CT134-135 locus of Chlamydia trachomatis.
- To determine the stability and mutation patterns of CT134 and CT135 in different C. trachomatis serovars and passage histories.
- To elucidate the selective pressures acting on CT135 in vitro and in vivo.
Main Methods:
- Targeted next-generation sequencing of the CT134-135 locus was employed.
- Analysis included reference strains and clinical isolates of C. trachomatis.
- In vitro serial passage experiments were conducted on a serovar K isolate.
Main Results:
- The CT134 gene demonstrated high stability across all examined C. trachomatis serovars.
- CT135 showed significant polymorphism, with mutations often leading to gene disruption, particularly in high-passage reference ocular and non-LGV genital serovars.
- In low-passage ocular clinical isolates, CT135 was frequently disrupted, while it remained largely intact in genital clinical isolates. In vitro passage led to rapid CT135 disruption, contrasting with CT134's stability.
Conclusions:
- CT134 is a highly conserved gene in C. trachomatis.
- CT135 is subject to strong positive selection in vivo for genital serovars and negative selection in vitro, explaining its observed mutation patterns.
- The differential genetic behavior of CT135 highlights its role in C. trachomatis adaptation and pathogenesis.
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