A new in vivo model to study the interactions between intracellular bacteria with their host

What is it about?

Chlamydia pneumoniae and Chlamydia trachomatiss are two closely related human pathogens. They are structurally unique bacteria which can only multiply inside eukaryotic cells. The challenging feature of chlamydial infections is their tendency to persistence, a response to environmental stress factors (such as host immune response or antibiotic treatment), which makes the eradication of the infection with standard antibiotics very difficult. The molecular mechanisms of chlamydial persistence are poorly understood, which limits also the development of new treatment strategies for their effective eradication. In this work, we demonstrate the ability of C. pneumoniae and C. trachomatis to establish an infection in the nematode C. elegans, as well as the use of the newly developed infection model for assaying a golden-standard antichlamydial drug azithromycin and a plant extract with previously reported in vitro antichlamydial activity. Using the nematode lifespan and bacterial genome copy numbers as endpoints, the data demonstrates a compromized efficacy of azithromycin in protecting the worms against persistent chlamydial infection. On the other hand, the model gave valuable insights to the mechanism of action of the studied plant extract, as it was found to activate Skn-1, the worm homolog of Nrf-2 transcription factor and worms defective in SEK-1, an upstream regulator of Skn-1, were not protected from the infection by the extract treatment.

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Why is it important?

fading efficacy of antibiotics forces us to search for antibacterial agents acting through novel molecular mechanisms. Finding new antibacterial drug targets has proven difficult, owing to poorly understood pathogen-host interactions and in particular, lacking information about the target essentiality in vivo, ie. in the context of an infection in a living host. The nematode C. elegans can offer valuable insights to these questions and therefore help in not only understanding the basic biology of intracellular bacterial infections but also guide the way towards new antibacterial therapies.fading efficacy of antibiotics forces us to search for antibacterial agents acting through novel molecular mechanisms. Finding new antibacterial drug targets has proven difficult, owing to poorly understood pathogen-host interactions and in particular, lacking information about the target essentiality in vivo, ie. in the context of an infection in a living host. The nematode C. elegans can offer valuable insights to these questions and therefore help in not only understanding the basic biology of intracellular bacterial infections but also guide the way towards new antibacterial therapies.

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