Corporate Banner
Satellite Banner
Mass Spectrometry
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Antibiotic Finds Novel Way of Sn(e)aking Across Membranes

Published: Thursday, July 04, 2013
Last Updated: Thursday, July 04, 2013
Bookmark and Share
Researchers investigating the targeting of bacteria by protein antibiotics have discovered a new mechanism by which they can snake their way into bacterial cells.

Professor Colin Kleanthous and his research group, together with colleagues in the chemistry department at the University of Oxford and at Birkbeck College, University of London, describe the snaking mechanism in their recent paper in Science (see references below).

The previously unknown process by which these protein antibiotics gain entry into bacteria could be relevant to other systems where proteins cross membranes. The work will also help studies exploring whether these antibiotics, which target closely related bacteria, have clinical potential.

The antibiotics, colicins, are part of a large family of antibacterial proteins that target the gut bacterium Escherichia coli. Similar antibiotics are produced by many other bacteria, including many pathogens, and are used to attack neighbouring bacteria competing for the same resources.

They bind to proteins on the cell surface and then assemble a complex nanomachine or 'translocon' that links the outside of the cell to the inside. Once these connections are made, the colicin is able to move into the cell where it delivers a toxic payload.

Scientists knew colicin used a protein called OmpF on the outside of the target bacteria cell as part of this process but until now, the details of how the colicin exploited OmpF were unknown.

The work from Professor Kleanthous and colleagues sheds light on the process, revealing the surprising 'snaking' mechanism.

The discovery required important technical developments in a number of areas.

One of the major advances was in mass spectrometry, in collaboration with Professor Carol Robinson and Dr Jonathan Hopper in the University of Oxford chemistry department.

"The work we've done together is really pushing the boundaries in terms of membrane protein mass spectrometry", said Professor Kleanthous. "The mass spec result was amazing - it had never been done before."

The group suspected that colicin threaded through two of OmpF's three holes, so designed a new technique sensitive enough to detect if part of the colicin molecule was occupying them.

"The mass spec approach showed that we could measure the mass of the peptide inside the holes", said Professor Kleanthous. "The peptide is only around 1% of the total mass, but we can detect this because the resolution of the technique is so good."

By engineering a mutation in colicin they were able to keep the translocon tethered in place in order to capture, purify and analyse it.

This revealed that to form the translocon colicin had indeed snaked through two of OmpF's holes.
"We found that colicin is tethered to two holes in a three-hole protein", said Professor Kleanthous. "The surprise is that the colicin not only goes into the cell by one of the holes of OmpF but also comes back out again through a second hole."

When viewed under an electron microscope the researchers saw that the threaded colicin allows another protein within the cell membrane to be held in place, making it easier to continue colicin's journey into the bacterium.

This mechanism explains how disordered proteins can burrow their way through narrow pores, as well as pass a charged signal into a cell.

Now that the group have started to piece together the molecular interactions between components of the translocon, they are keen to fill in more of the details.

"We want to find out exactly how the colicin sneaks its way in and out of OmpF and to see if this mechanism occurs in colicins that target pathogenic bacteria", said Professor Kleanthous. "We'll be focusing on all the components of the translocon, ultimately trying to assemble them in a reconstituted system in vitro."


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,900+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Top 10 Life Science Innovations of 2016
2016 has seen the release of some truly innovative products. To help you digest these developments, The Scientist have listed their top picks for the year.
Hunting the Missing Link Between Genetics and the Environment
The International Phenome Centre Network (IPCN) works to transform healthcare through phenomics - the dynamic interactions between our genes and our environment.
Cocaine Test Could Lead to Rapid, Low Cost Roadside Testing
Scientists develop urine and oral fluid diagnostic test for cocaine, utilising a compact mass spectrometer.
The Benefits of a Mediterranean-style Diet
A Western-style diet, with more omega-6 fatty acids than the Mediterranean, dysregulates lipid signaling in aged mice and promotes inflammation.
Peer Review is in Crisis, But Should be Fixed, Not Abolished
After the time to get the science done, peer review has become the slowest step in the process of sharing studies, and some scientists have had enough.
Rapid Identification of Illicit Designer Drugs
New technique can identify commonly used illicit compounds in as little as 15 seconds.
Enhancing On-line Biological Sample Processing
New techniques are required to meet emerging demands on biopharmaceutical analysis.
Early Warning System for Colorectal Cancer
Potential new diagnostic tool identified for the second most common cancer in the world.
Scientists Develop a Novel Method to Benchmark and Improve the Performance of Protein Measurement Techniques
A wide range of laboratories around the world are benefiting from this work, which enables researchers to analyze or compare the results of quantitative proteomics assays in a standardized way.
Amyloid Study Pinpoints Protein Culprits
A five-year trial at a Brisbane Hospital has increased the accuracy of diagnosing patients with amyloidosis, a group of rare and incurable diseases caused by abnormal protein deposits in tissues and organs.
Scroll Up
Scroll Down
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!