Chlamydia infection may pave way for cancer via dna damage


Chlamydia infection may pave way for cancer via dna damage

New research from Germany suggests that persistent infection by Chlamydia may pave the way for cancer: not only does the pathogen cause mutations in host cell DNA, it also inhibits the cellular mechanisms that attempt to repair the damage.

The researchers, from the Max Planck Institute for Infection Biology in Berlin (MPIIB), write about their findings in a paper published online in the journal Cell Host & Microbe on 12 June.

A Leading Cause of Sexually Transmitted Disease

The bacterium Chlamydia trachomatis is a leading cause of sexually transmitted disease that infects over 90 million people worlwide every year.

Chlamydia infection often goes unnoticed, can persist for years with little or no symptoms, and can damage women's reproductive organs.

As well as this, the bacterium is proving increasingly stubborn to shift: antibacterial drugs are often no longer strong enough to eradicate it completely, so it goes into persistent mode, leading to chronic infection with no symptoms.

Chlamydia Uses Various Tactics to Ensure Survival

In some respects we already know quite a lot about the behavior of the pathogen.

For instance, we know that Chlamydia uses "Trojan horse" tactics to enter host cells unnoticed.

And we also know that a protein called Pgp3 enhances Chlamydia's ability to enter host cells unnoticed and then evade host defences.

Plus, we know that to ensure survival, Chlamydia needs to make the most of the resources inside the host cell, which is where the bacterium spends most of its life.

Once inside the host cell, the pathogen goes about changing the cell to make itself at home. It re-arranges host cell processes to favour its own growth and proliferation. But it's not clear how this affects the cell's normal functions and whether it leads to disease.

However, there is evidence that it might: there is a growing mountain of epidemiological data linking Chlamydia infections to the development of cervical and ovarian cancer development. But exactly how this might come about has been somewhat of a mystery - until now.

Chlamydia Causes Lasting Genetic Damage to Host Cells

In this new study, the researchers show that Chlamydia makes a long-lasting impression on the genome and epi-genome of host cells. Such changes are increasingly implicated in the development of a range of cancers.

They found host cells acutely and persistently infected with Chlamydia had increased levels of different kinds of DNA breaks.

In normal cells, when these types of breaks occur, they either go into cell suicide mode (apoptosis, where the cell is removed, broken down and its material parts recycled) or DNA repair mode.

In DNA repair mode, special proteins trigger a process called DNA Damage Response which attempts to reseal the broken strands of DNA to make sure the correct sequence of genetic code is restored (so when the cell replicates it produces healthy daughter cells).

But not only did the researchers find that Chlamydia-infected cells had altered DNA, but also that their DNA Damage Response didn't work properly: so the broken DNA didn't get repaired in those cells that didn't go down the cell suicide route.

Chlamydia disrupted the host cell DNA Damage Response by stopping key proteins from reaching the sites of DNA damage.

Chlamydia Damage to Cells Is Similar to that Which Leads to Cancer

Thus Chlamydia-infected, damaged cells that did not go down the cell suicide route continued to proliferate, passing on the DNA damage, and also spurred by some extra pro-survival signals activated in the host cell by the pathogen.

The result is an increasing population of rogue host cells that have escaped the normal mechanisms that ensure faulty DNA is not replicated: a hallmark of cancer.

The discovery is important because if it is established that an infection leads to cancer, then vaccination to prevent the infection, or antibiotics to eliminate it, may also prevent the cancer.

Such preventive methods are already working with other cancer-causing agents such as Human Papiloma Virus (HPV) and Helicobacter pylori, which can cause cervical and gastric cancer, respectively.

However, the path from infection to cancer needs to be firmly established before such a strategy can be considered in the case of Chlamydia.

The study is but one piece of the jigsaw that must be assembled to reveal such a path, say the researchers in a press statement.

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