Chlamydia trachomatis: a model for intracellular bacterial parasitism

Abstract

Chlamydia comprises a diverse group of obligate intracellular bacteria that cause infections in animals, including humans. These organisms share fascinating biology, including distinct developmental stages, non-canonical cell surface structures, and adaptations to intracellular parasitism. Chlamydia trachomatis is of particular interest due to its significant clinical importance, causing both ocular and sexually transmitted infections. The strain L2/434/Bu, responsible for lymphogranuloma venereum, is the most common strain used to study chlamydial molecular and cell biology because it grows readily in cell culture and is amenable to genetic manipulation. Indeed, this strain has enabled researchers to tackle fundamental questions about the molecular mechanisms underlying Chlamydia's developmental transitions and biphasic lifecycle and cellular adaptations to obligate intracellular parasitism, including characterizing numerous conserved virulence genes and defining immune responses. However, L2/434/Bu is not representative of C. trachomatis strains that cause urogenital infections in humans, limiting its utility in addressing questions of host tropism and immune evasion in reproductive organs. Recent research efforts are shifting toward understanding the unique attributes of more clinically relevant C. trachomatis genovars.

Keywords: Chlamydia; bacterial persistence; genetic tools; host tropism; inclusion membrane proteins (Incs); lateral gene transfer; model organism; obligate intracellular pathogen.

Fig 1

C. trachomatis L2/434/Bu as a model organism for chlamydial research. This figure highlights three key aspects of C. trachomatis L2/434/Bu that have significantly advanced our understanding of chlamydial biology. The obligate intracellular lifecycle and stress response mechanisms, which are largely conserved throughout the Chlamydia genus, have been studied extensively using L2/434/Bu, making it a foundational model for these traits. Furthermore, the development of genetic tools, predominantly achieved in L2, has been instrumental in advancing Chlamydia research and can be adapted for studying other species. Created in https://BioRender.com.

Fig 2

Limitations of C. trachomatis L2 as a model for chlamydial diseases. Traits conserved within the Chlamydia genus (left side) highlight why C. trachomatis L2/434/Bu is an effective model for studying chlamydial biology, including its unique biphasic obligate intracellular lifecycle, similarities between genomes, and preferential tropism to mucosal epithelia. In contrast, there are limits to this model based on distinctive characteristics that each Chlamydia species and strain possesses (right side), encompassing regions of genome variability and host and tissue tropisms. Created in https://BioRender.com.