Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Yale scientists ’see’ basis of antibiotic resistance

25.04.2005


Using X-ray crystallography, researchers at Yale have "seen" the structural basis for antibiotic resistance to common pathogenic bacteria, facilitating design of a new class of antibiotic drugs, according to an article in Cell.



In recent years, common disease-causing bacteria have increasingly become resistant to antibiotics, such as erythromycin and azithromycin. Although the macrolide antibiotics in this group are structurally different, all work by inhibiting the protein synthesis of bacteria, but not of humans. They bind tightly to an RNA site on the bacterial ribosomes, the cellular machinery that makes protein, but not to the human ribosomes.

Bacteria can become resistant to antibiotics in several different ways. When bacteria mutate to become resistant to one of these antibiotics, they usually are resistant to all antibiotics in the group.


Studies led by Sterling Professors Thomas A. Steitz and Peter B. Moore in the departments of molecular biophysics and biochemistry and chemistry at Yale illuminate one of the ways that bacteria can become resistant to macrolide antibiotics.

"A major health concern of antibiotic resistance is that two million people every year get infections in hospital facilities and 90,000 per year die from them," said Steitz. "Macrolide-resistant Staphylococcus aureus is the most common of these infections."

Some of the clinically important bacteria are resistant because of mutation of a single nucleotide base, from an A to a G, in the site where macrolide antibiotics bind to the ribosome. The Yale group was able to "see" structural alterations when antibiotics were bound to ribosomes with different sensitivity to the drugs because of mutation.

They can now explain why that mutation has the effect that it does. "The mutant G has an amino group that pokes into the center of the macrolide ring, causing it to back off the ribosome by an Angstrom or so," said Steitz.

The change of that one base in the ribosomal RNA reduced the ability of the antibiotic to bind by a factor of 10,000.

Mutation of this type happens naturally, but rarely -- only one in 100,000 to one in 10,000,000 bacterial mutations will cause this kind of resistance. However, each bacterium can divide as often as every 20 minutes, allowing one with a resistant mutation to rapidly cause a dangerous infection.

Steitz and Moore are among the co-founders of Rib-X, a New Haven-based start-up company that has exclusive license to the high-resolution crystal structure of the ribosome they revealed. Rib-X is utilizing this information to create new antibiotics; they project Phase-I trials of their first drug to begin in early 2006.

Daqi Tu, a student, and Gregor Blaha, a postdoctoral fellow in molecular biophysics and biochemistry and associate of the Howard Hughes Medical Institute, are co-authors on the study.

Funding for this research was obtained from the National Institutes of Health and the Agouron Institute.

Janet Rettig Emanuel | EurekAlert!
Further information:
http://www.yale.edu

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>