Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

In the ring: Researchers fighting bacterial infections zero in on microorganism's soft spots

14.07.2010
Team maps targets with hopes of blocking reproduction and rendering infection down for the count

In any battle, sizing up one's opponent is a critical first step. For researchers fighting a bacterial infection, that means assessing every nook and cranny of the malicious microorganism and identifying which ones to attack.

At the Center for Biological Research of the Spanish Research Council in Madrid, scientists are devising maneuvers they hope will take out bacteria at their molecular knees, and they are optimistic a recent advance will help yield therapies for a number of infections, including antibiotic-resistant strains delivering blow after blow in hospitals across the globe.

In a Journal of Biological Chemistry "Paper of the Week," Dr. Antonio J. Martín-Galiano and professor José M. Andreu are reporting that they have mapped out a promising target for a strategic hit after carefully analyzing a protein that bacteria need in order to reproduce and further infect hosts.

"Bacterial infections are a threat around the globe. This includes not only people in underdeveloped countries, but also patients compromised by the emergence of new antibiotic-resistant pathogens in First World communities and hospitals," Martín-Galiano said. "There is an urgent need to find new bacterial targets and new antibiotics with which to fight infections. Our work, by providing basic insight into the inner functional mechanisms of one new target, cell-division protein FtsZ, may be a little bit of help."

A bacterial cell reproduces through a process called binary fission. First, the parent cell's DNA duplicates so that the future daughter cell will have all the correct genetic information. Then, special building-block proteins, known as FtsZ, move inside the parent cell toward the center and get to work building scaffolding for the construction of a new dividing ring. FtsZ is believed to generate constriction force, while the cell wall keeps growing toward the center of the cell. Finally, the ring tightens like a noose and splits the cell in two, each with identical DNA.

Martín-Galiano and Andreu focused on how the FtsZ building blocks operate, hoping to understand better how their ever-changing shapes affect the creation of the cell-dividing wall. After all, if FtsZ could be manipulated, perhaps cell division, and replication of the bacteria, could be halted.

Scientists have understood for some time now that, during cell division, the FtsZ filaments assemble and disassemble repeatedly. When the filaments are in the assembly phase, they line up in a relatively straight fashion, and, when they are in the disassembly phase, they become somewhat curved.

But what has remained a mystery is what spurs the change between FtsZ's straight and curved states of being, and their team set out to answer the question: What makes FtsZ shape up just right for the job?

"That would be what is called the FtsZ switch, and it remained to be revealed," Andreu said.

That is, until now.

Andreu's team created computer models that predict the movements of the FtsZ molecules and from that data gleaned which pivot points and hinges allow them to change shape and assemble into straight and curved filaments. They then mutated a number of those moving parts, by switching up their constituent amino acids, and observed how the assembly-disassembly cycle was affected.

"This would be analogous to modifying gears of clockwork in a mechanical watch and then looking at the effects on its functioning," Andreu explained.

Some of the tweaks to the protein's amino acids didn't make much of a difference, and the FtsZ molecules went on with their business as normal: binding to each other, gobbling up energy molecules, breaking apart and repeating those steps about every 10 seconds. But other mutations made a world of difference and shelved FtsZ's cell-wall construction plans entirely.

"Several of the mutations blocked the transition of curved to straight FtsZ and produced spiral filaments instead of straight ones," Andreu said, and spiral filaments can't help the cell to divide. "Interestingly, these critical changes clustered around a cleft between two main moving parts of FtsZ, where a new antibacterial compound is thought to bind."

That compound, known as PC190723, was discovered by researchers at Prolysis Ltd. in 2008 in the United Kingdom and was shown to have antibacterial activity against several microbes, including the quite drug-resistant and virulent staph infection known as methicillin-resistant Staphylococcus aureus, or MRSA.

Now, with the new insights from Andreu's team, scientists are in a better position to pursue other compounds that might inhibit FtsZ's ability to build the bacterial cell wall by binding to the cleft between the two parts of FtsZ with greater specificity or efficiency – essentially mucking up FtsZ's gears.

The researchers performed their analysis and experiments on FtsZ from the archaebacterium Methanococcus jannaschii, which thrives in extreme environments, such as at hydrothermal vents on the seafloor.

"Given the large degree of structural similarity between most FtsZ proteins, including FtsZ from the pathogens that cause tuberculosis, pneumonia and other human infections, we hope that the results may be extrapolated to the FtsZ from pathogenic bacteria," Andreu said.

Andreu and Martín-Galiano's team also included Rubén M. Buey, a former group member who participated in the design of the project and analyzed the results, and Marta Cabezas, who purified many of the FtsZ protein variants.

The team's research was funded by the Spanish Ministry of Science, the Madrid Community and the Federation of European Biochemical Societies. The resulting "Paper of the Week" was published on the Journal of Biological Chemistry's website May 15 and will appear in the July 16 issue.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions. For more information about ASBMB, visit www.asbmb.org.

Angela Hopp | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>