Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tuberculosis: Agents in MycPermCheck

14.01.2013
About two million people worldwide die of tuberculosis each year. There is an urgent need for new drugs and they will probably get easier to find in future – thanks to the new model MycPermCheck, which was developed at the University of Würzburg.
Tuberculosis is caused by a pathogen called Mycobacterium tuberculosis. If differs from many other types of bacteria in that it possesses a particularly thick cell wall. It is nearly impervious to foreign substances so that the pathogen is fairly drug-resistant.

"Many agents that could otherwise be highly effective fail to penetrate the thick cell wall," explains Professor Christoph Sotriffer of the Institute of Pharmacy at the University of Würzburg. Because of this barrier, many drugs do not reach their destination – the interior of the bacteria – or they arrive in such low concentrations as to be ineffective.

What gets agents through the cell wall?

Which conditions does an agent have to satisfy in order to pass easily through the cell wall of the tuberculosis pathogen? Previously, this question could not be answered by scientists. University of Würzburg pharmacologists and bioinformaticians have just come up with some first answers. Their results are published in the journal "Bioinformatics".

Christoph Sotriffer's colleagues, Benjamin Merget and David Zilian have examined 3815 substances effective against mycobacteria, comparing them with numerous ineffective or randomly selected substances. In their analyses, they identified several physico-chemical properties that are quite useful to predict whether or not a given molecule will be able to penetrate the cell wall of the pathogen. Such properties include the size of the hydrophobic area or the number of hydrogen bonding sites.

How effectiveness can be estimated

The scientists have developed the statistical model "MycPermCheck" on the basis of their findings: It can be used to estimate the probability of organic molecules with a relative molecular mass of up to approx. 500 being able to pass through the cell wall of mycobacteria and take effect in the bacterium. The model is available as a free web service on the home page of Sotriffer's study group.

"For the first time, MycPermCheck makes it possible to focus the search for agents against mycobacteria on such chemical compounds that have a high probability of being able to get inside the bacterium," the professor explains. This could be used to conduct virtual and experimental screenings more efficiently and in a more targeted way. The model can also be used to check whether any newly developed substances have the desired properties. "If this is not the case, you can try to achieve this by means of a targeted molecular design," says Sotriffer.

Why screenings are getting more effective

MycPermCheck is not a procedure with which the permeability of the bacterial cell wall can be calculated with exact precision, which point the developers emphasize. All users are advised to be aware of this. The model only increases the probability of picking out exactly the molecules that are suited to overcome the mycobacterial cell wall, when selecting from a great number of chemical compounds.

Professor Sotriffer: "Since several hundreds of thousands up to several millions of compounds are typically involved in a screening, it would already be a success if we were able to restrict the search for new agents to, say, the best ten percent of molecules that have a high probability of getting easily inside the bacterium. This would somewhat facilitate the difficult process of developing new drugs against tuberculosis."

MycPermCheck in the Internet: http://www.mycpermcheck.aksotriffer.pharmazie.uni-wuerzburg.de

The new findings were discovered at the Collaborative Research Center 630 (Recognition, Preparation and Functional Analysis of Agents against Infectious Diseases) of the University of Würzburg. The research is funded by the German Research Foundation.

Facts on tuberculosis

Tuberculosis, also known as consumption, is the most common bacterial infectious disease worldwide. More than eight million people contract the disease each year, most of them in Sub-Saharan Africa, Asia and Eastern Europe. According to the Robert Koch Institute, between 4000 and 5000 new infections were annually reported in Germany in recent years.

Mycobacterium tuberculosis bacteria in a stained electron microscopic image.

Source: Public Health Image Library / Janice Haney Carr

The pathogens mainly attack the lungs. The consequences are constant coughs with sputum, weight loss and profuse night sweats. In serious cases, the sputum is blood-stained and underweight as well as severe anemia occur. If left untreated, the disease often leads to death.

Drugs that are able to cure tuberculosis have already been available since the middle of the 20th century. However, the treatment is complicated: It takes several months and requires a combination of at least four substances. Furthermore, several strains of the pathogen have become resistant to the drugs. We don't have a lot of viable alternatives, since no new drugs have been developed for decades.

"MycPermCheck: the Mycobacterium tuberculosis permeability prediction tool for small molecules", Benjamin Merget, David Zilian, Tobias Müller, and Christoph A. Sotriffer, Bioinformatics 2013, 29 (1): 62-68; DOI: 10.1093/bioinformatics/bts641

Contact person
Prof. Dr. Christoph Sotriffer, Institute of Pharmacy and Food Chemistry, University of Würzburg, T +49 (0)931 31-85443, sotriffer@uni-wuerzburg.de

Gunnar Bartsch | idw
Further information:
http://www.uni-wuerzburg.de

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

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...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

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...

Im Focus: Breaking the bond: To take part or not?

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...

Im Focus: New 2D Spectroscopy Methods

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....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

NSF-supported researchers to present new results on hurricanes and other extreme events

19.07.2018 | Earth Sciences

Scientists uncover the role of a protein in production & survival of myelin-forming cells

19.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>