Chlamydia trachomatis escapes recognition by the host by cloaking itself in fat-rich structures


The Chlamydiae learned to parasitize eukaryotic cells half a billion years ago by reprogramming cellular functions from within.
In humans today, chlamydial infections are responsible for a range of ailments from sexually transmitted infections to atypical pneumonias to chronic severe disorders such as pelvic inflammatory disease and atherosclerosis.

The Centers for Disease Control says that Chlamydia trachomatis is the most common sexually-transmitted infection in the US, with three million new cases a year.

Chlamydia gets around because it knows its hosts so well. It's an "obligate intracellular parasite" which means that it relies on its eukaryotic host for everything from reproduction to synthesizing ATP, all while living inside a membrane-bounded vacuole that provides a protected, fertile environment for the bacteria to grow and multiply. Because lipid acquisition from the host is necessary for chlamydial replication, these pathogens are essentially lipid parasites.

Lipid droplets are fat-rich structures found in all eukaryotic cells.
In humans, lipid droplets are abundant in adipocytes, our professional fat storage cells, where they have traditionally been regarded as passive storage depots of excess fat. However, recent studies have reassessed their role.
Lipid droplets are now known to be motile, dynamic and enriched for proteins known to regulate lipid synthesis, membrane traffic and cell signaling.

The discovery of an interaction between lipid droplets and Chlamydia was made as Yadunanda Kumar and Raphael Valdivia, at Duke University Medical Center, performed the genetic equivalent of an end-run.
Chlamydia is not amenable to direct genetic manipulation so the researchers moved the pathogen's genes elsewhere, inserting them into the eukaryotic cells of baker's yeast. The resulting chlamydial proteins were screened for those that targeted to yeast intracellular organelles.
They identified four proteins that were specifically recruited to lipid droplets.

The researchers found that Chlamydia not only directs lipid droplets to its protective vacuole but also causes the proliferation of new lipid droplets on the host. The co-option of lipid droplets appears to be essential for Chlamydia pathogenesis. When the researchers used drugs to inhibit lipid droplet formation in the host, they sharply impaired bacterial growth.

That finding suggests an entirely novel pathogenic mechanism. " We propose that Chlamydia use lipid droplets in a previously unknown pathway for lipid acquisition," says Kumar. "Alternatively, it is possible that the recruitment of lipid droplets constitutes an example of 'organelle mimicry' where Chlamydia escapes recognition by the host by cloaking itself in these fat-rich structures."

Understanding host lipid transport by Chlamydiae may have further implication for chronic infections, the researchers say.
For example, lipid-rich macrophages ( "foam cells" ) are a symptom in chlamydial pneumonia. Because foam cells are a key element in development of atherosclerosis, lipid droplet co-option also suggests a possible explanation for the association between chlamydial infections and heart disease.

Source: American Society for Cell Biology, 2005


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