Chlamydia are the triggers for a whole range of serious diseases. At the same time, the bacteria are dependent for their survival on support from the cells they attack. The tricks they use here have been examined more closely by microbiologists from the University of Würzburg.
Bacteria of the Chlamydia trachomatis strain are responsible for a number of serious diseases in humans. A chlamydia infection is among the most common sexually transmitted diseases in the world. Current estimates suggest that, depending on the age group, up to ten percent of the population is infected with the pathogens worldwide.
Without treatment, these bacteria in women often cause the fallopian tubes to become blocked, which can result in ectopic pregnancies or infertility. Recent findings even indicate that chlamydia infections promote the development of ovarian cancer. Men can become infertile after infection.
A further consequence of a chlamydia infection arises mainly in tropical countries: there the bacteria attack the eyes and can lead to blindness. Around 150 million people are said to be suffering from this. Other strains can trigger pneumonia and are suspected of causing diseases such as atherosclerosis and Alzheimer’s disease.
The host looks after his guest
However, for chlamydia to be able to live and multiply, they are dependent on support from their “victim”. As the analysis of the Chlamydia trachomatis genome shows, the bacterium is entirely devoid of numerous metabolic processes and some exist only in fragments. For this reason, the bacterium needs to be supplied by its host cell with the necessary nutrients – nucleic acids, proteins, and lipids – continuously throughout its development cycle. It therefore has a strong interest in ensuring that the cell it has attacked stays intact and alive.
Professor Thomas Rudel, Chairman of the Department of Microbiology at the University of Würzburg, and his team have spent quite some time examining how chlamydia manage this. The scientists have now uncovered new details of the interaction between Chlamydia trachomatis and its host cell. They present their findings in the latest issue of Cell Reports.
Chlamydia prevent the cells from committing suicide
“When chlamydia attack a cell, this always causes considerable damage to the genetic material of this cell,” says Thomas Rudel. Normally, this would mean that the cell automatically “shuts down”, so to speak, or even initiates programmed cell death, known as apoptosis. This is how an organism prevents malfunctioning cells from multiplying in an uncontrolled manner and causing major damage. But in the case of a chlamydia infection this does not happen; it would appear that the bacterium is capable of preventing programmed cell death in the cell attacked.
“We were able to show that chlamydia deactivate the tumor suppressor protein p53 in the cells they have attacked and set in motion a process that ends up repairing the damage to the genetic material,” says Rudel. “Guardian of the genome”: the p53 protein is also known by this name. It has the ability to interrupt the cell cycle in damaged cells and, by doing so, to prevent the cell from dividing. This gives the cell more time to repair damage to the genetic material or to put itself out of action if it is beyond repair.
In a series of experiments, the Würzburg microbiologists were able to shed light on details of the relationship between the bacterium and the tumor suppressor. Their findings include the following:
• Since a chlamydia infection is always accompanied by damage to the genetic material, the bacteria prevent the tumor suppressor protein p53 from doing its job. In their experiments, the scientists did not manage even once to initiate cell death when administering high doses of a substance that is damaging to genetic material to cells attacked by chlamydia.
• If the researchers kept the concentration of p53 artificially high in infected cells, the chlamydia were no longer able to develop. They stayed at a stage in their lifecycle at which they are not infectious.
• How p53 keeps chlamydia in check is unclear. As it recently came to light that the protein influences a number of metabolic processes, including glycolysis and glucose transport, the Würzburg microbiologists also examined this aspect. After all, chlamydia are reliant on their host cell to supply them with glucose. However, a direct correlation could not be confirmed.
• On the other hand, the scientists were able to identify a mechanism elsewhere that enables the bacteria and the tumor suppressor protein to interact with one another: glucose-6-P-dehydrogenase – a key enzyme within the pentose phosphate cycle. If the researchers blocked this enzyme and, with it, the entire cycle, the growth of the chlamydia was curbed dramatically. However, if they stimulated the cycle, the bacteria continued to grow even if the concentration of p53 in the host cells was high.
“Our findings show two things very clearly. Firstly, chlamydia deactivate the tumor suppressor protein p53 so that they can actually multiply in the infected cell. The fact that they have to disable one of the main tumor suppressors to do this might explain the correlation between chlamydia infections and tumor development,” says Thomas Rudel. Secondly, the significance of the pentose phosphate cycle has been revealed – not just for repairing the genetic material, but also for optimally supplying the bacteria with vital nutrients.
Siegl et al., Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection, Cell Reports (2014), http://dx.doi.org/10.1016/j.celrep.2014.10.004
Prof. Dr. Thomas Rudel, Department of Microbiology, T +49 (0)931 31-84401, Thomas.Rudel@biozentrum.uni-wuerzburg.de
Gunnar Bartsch | idw - Informationsdienst Wissenschaft
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences