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

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
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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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 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.

Related Content

Protective Proteins Reduce Damage to Blood Vessels
Proteins found blood have been shown to reduce damage caused to blood vessels as we age, and in conditions such as atherosclerosis and arthritis.
Thursday, May 22, 2014
Proteomics Tool Points to New Malaria Drug Target
BBSRC-funded scientists have taken an important step towards new malaria treatments by identifying a way to stop malaria parasites from multiplying.
Monday, December 23, 2013
Prions, vCJD and the Immune System Relay
BBSRC is helping to shed new light on variant Creutzfeldt-Jakob disease.
Friday, December 06, 2013
Scientists Identify Key Protein in Communication Between Brain Cells
Scientists are a step closer to understanding how some of the brain's 100 billion nerve cells co-ordinate their communication.
Friday, November 29, 2013
New Technique for Developing Drugs
An international team of researchers have created a new drug for possible use against heart disease, inflammation and other illnesses.
Monday, November 18, 2013
New Screening Technique Paves the Way for Protein Drugs from Bacteria
Scientists have developed a cheaper, more efficient technique for developing complex protein drugs from bacteria.
Monday, June 10, 2013
Researchers Pair Experiments with Computer Models to Peer into Cells
BBSRC-funded researchers have developed a new strategy that can give scientists a better insight into how complex molecular machineries function in living cells.
Wednesday, March 20, 2013
Vaccine Production in Plants Nets Scientist Innovator of the Year 2012
Innovation could allow quicker vaccine development to combat pandemics.
Friday, March 30, 2012
Researchers Visualise Herpes Virus' Tactical Manoeuvre
For the first time, researchers have developed a 3D picture of a herpes virus protein interacting with a key part of the human cellular machinery, enhancing our understanding of how it hijacks human cells to spread infection and opening up new possibilities for stepping in to prevent or treat infection.
Thursday, January 06, 2011
DNA Sequencing Pioneer Named BBSRC Innovator of the Year 2010
Prof. Shankar Balasubramanian has won £10,000 in recognition of his work on Solexa sequencing.
Tuesday, March 23, 2010
UK Bioscience Sparkles with New Diamond Fellowship
UK bioscience has received a major boost following the announcement of 16 new fellowships by the Biotechnology and Biological Sciences Research Council (BBSRC) including the first ever Diamond Fellowship, so named because the post will be based at the new Research Complex at Harwell, adjacent to the Diamond Light Source in Oxfordshire - the UK national synchrotron facility.
Tuesday, July 21, 2009
Scientific News
Key to Natural Detoxifier’s Reactivity Discovered
Results have implications for health, drug design and chemical synthesis.
New Protein Found in Immune Cells
Immunobiologists from the University of Freiburg discover Kidins220/ARMS in B cells and demonstrate its functions.
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
How a Molecular Motor Untangles Protein
Diseases such as Alzheimer’s, Parkinson’s and prion diseases, all involve “tangled” proteins.
Compound Doubles Up On Cancer Detection
Researchers have found that tagging a pair of markers found almost exclusively on a common brain cancer yields a cancer signal that is both more obvious and more specific to cancer.
How Cell Growth Triggers Cell Division
Researchers in Jan Skotheim's lab have discovered a previously unknown mechanism that controls how large cells grow, an insight that could one day provide insight into attacking diseases such as cancer.
Probing the Forces Involved in Creating The Mitotic Spindle
Scientists at The Rockefeller University reveal new insights into the mechanical forces that govern elements of the mitotic spindle formation.
Identifying Cancer’s Food Sensors May Help to Halt Tumour Growth
Oxford University researchers have identified a protein used by tumours to help them detect food supplies. Initial studies show that targeting the protein could restrict cancerous cells’ ability to grow.
Specific Variations in RNA Splicing Linked to Breast Cancer
Researchers have identified cellular changes that may play a role in converting normal breast cells into tumors. Targeting these changes could potentially lead to therapies for some forms of breast cancer.
Thousands of Protein Interactions Identified
Thanks to the work by Utrecht University researcher Fan Liu and her colleagues, it is now possible to map the interactions between proteins in human cells.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos