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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>