Nav: Home

Protein synthesis: Ribosome recycling as a drug target

December 05, 2016

Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have elucidated a mechanism that recycles bacterial ribosomes stalled on messenger RNAs that lack termination codons. The protein involved provides a potential target for future antibiotics.

So-called multidrug-resistant bacteria - strains that have become resistant to conventional antibiotics - pose an increasingly serious medical problem, which underlines the urgent need to develop new antibiotics that attack novel targets. "Many of the most effective antibiotics act by inhibiting various steps in protein synthesis on bacterial ribosomes," as LMU biochemist Daniel Wilson points out. The search is now on for agents that interfere with aspects of the process that have so far been overlooked in this context. One of these processes is the recycling of stalled ribosomes. Wilson and his research group have just completed a comprehensive structural study of ribosome recycling. The results of the study, which appears in the leading journal Nature, may identify promising points of attack for future antibiotics.

Ribosomes are the organelles that translate the nucleotide sequences encoded in messenger RNA molecules (mRNAs) into the amino-acid sequences of the corresponding proteins. The ribosome "reads" the nucleotide sequence in a fixed direction and is released from the mRNA only when it reaches a defined termination signal. Errors in synthesis or processing may, however, lead to the production of mRNAs that lack termination signals, causing the ribosome to stall while still attached to the mRNA and the growing protein. Cells have evolved several ways of detaching stalled ribosomes from the truncated mRNAs and recycling them for re-use. Wilson's team has now employed cryo-electron microscopy to determine the structure of the bacterial recycling factor ArfA. Their analysis reveals how ArfA recognizes the stalled ribosome on a defective mRNA and recruits a so-called release factor, which detaches the incomplete protein. This then enables the stalled ribosome to be released from the mRNA in the normal manner by dissociation into its two component subunits. The subunits are then free to interact with another mRNA, thus allowing protein synthesis to proceed.

"Our results could facilitate the development of new antibiotics that act by inhibiting ArfA-mediated ribosome recycling," says Wilson. Since recycling of human ribosomes is dependent on factors that are unrelated to ArfA, such inhibitors should act specifically on the bacterial ribosome, and kill the bacterial cell by gradually cutting off the supply of free ribosomes.
-end-


Ludwig-Maximilians-Universität München

Related Antibiotics Articles:

Antibiotics: City dwellers and children take the most
City dwellers take more antibiotics than people in rural areas; children and the elderly use them more often than middle-aged people; the use of antibiotics decreases as education increases, but only in rich countries: These are three of the more striking trends identified by researchers of the NRW Forschungskolleg ''One Health and Urban Transformation'' at the University of Bonn.
Metals could be the link to new antibiotics
Compounds containing metals could hold the key to the next generation of antibiotics to combat the growing threat of global antibiotic resistance.
Antibiotics from the sea
The team led by Prof. Christian Jogler of Friedrich Schiller University, Jena, has succeeded in cultivating several dozen marine bacteria in the laboratory -- bacteria that had previously been paid little attention.
Antibiotics not necessary for most toothaches, according to new ADA guideline
The American Dental Association (ADA) announced today a new guideline indicating that in most cases, antibiotics are not recommended for toothaches.
Antibiotics with novel mechanism of action discovered
Many life-threatening bacteria are becoming increasingly resistant to existing antibiotics.
Resistance can spread even without the use of antibiotics
Antibiotic resistance does not spread only where and when antibiotics are used in large quantities, ETH researchers conclude from laboratory experiments.
Selective antibiotics following nature's example
Chemists from Konstanz develop selective agents to combat infectious diseases -- based on the structures of natural products
Antibiotics can inhibit skin lymphoma
New research from the LEO Foundation Skin Immunology Research Center at the University of Copenhagen shows, surprisingly, that antibiotics inhibit cancer in the skin in patients with rare type of lymphoma.
Antibiotics may treat endometriosis
Researchers at Washington University School of Medicine in St. Louis have found that treating mice with an antibiotic reduces the size of lesions caused by endometriosis.
How antibiotics help spread resistance
Bacteria can become insensitive to antibiotics by picking up resistance genes from the environment.
More Antibiotics News and Antibiotics Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.