Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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 3,300+ scientific posters on ePosters
  • More Than 4,900+ 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.

Related Content

UK-Brazil Wheat Research Projects Awarded £4M
£4M investment from BBSRC and Embrapa has been awarded to four Brazil-UK partnerships.
Wednesday, July 27, 2016
Protein Boosts Rice Yield by 54%
Over-expression of a natural protein in rice plants led to a 54% increase in crop yield and 40% increase in nitrogen-use efficiency.
Wednesday, July 27, 2016
A New £81.6M Food and Health Research Centre
The Quadram Institute is the name of the new centre for food and health research to be located at the heart of the Norwich Research Park, one of Europe’s largest single-site concentrations of research in food, health and environmental sciences.
Wednesday, February 17, 2016
Genome-Editing Position Statement
A group of leading UK research organisations has today issued an initial joint statement in support of the continued use of CRISPR-Cas9 and other genome-editing techniques in preclinical research.
Monday, September 07, 2015
Expanding the DNA Alphabet: 'Extra' DNA Base Found to be Stable in Mammals
A rare DNA base, previously thought to be a temporary modification, has been shown to be stable in mammalian DNA, suggesting that it plays a key role in cellular function.
Thursday, June 25, 2015
Global Food Security (GFS) Develops New Funding Programme
New programme of research to tackle resilience of the food system.
Tuesday, June 02, 2015
£4M to Fund Important Food Crops from BBSRC and NERC
Research projects designed with industry partners to maximize impact.
Tuesday, June 02, 2015
Controlling Leaf Blotch Disease In Wheat
Scientists have found a genetic mechanism that could stop the spread of a "devastating" disease threatening wheat crops.
Thursday, February 05, 2015
Rising Temperatures Predicted to Lower Wheat Yields
An international consortium of researchers has used big data sets to predict the effects climate change on global wheat yields.
Friday, December 26, 2014
New Test For Detecting Horse Meat
New test compares differences in chemical compositions of the fat found in meats.
Tuesday, December 02, 2014
UK And India Collaborate On Future-Proof Crops
Drought-tolerant tomatoes, improved wheat and grass pea could provide crops for the future.
Friday, November 28, 2014
Drugs Used to Treat Lung Disease Work With the Body Clock
Scientists from The University of Manchester have discovered why medication to treat asthma and pneumonia can become ineffective.
Thursday, August 14, 2014
Researchers Use ‘Big Data’ Approach to Map the Relationships Between Human and Animal Diseases
EID2 database used to prevent and tackle disease outbreaks around the globe.
Thursday, July 17, 2014
TGAC at the Forefront of Next Generation Sequencing Capability
The Genome Analysis Centre adds two Illumina HiSeq 2500 machines to its platform suite.
Thursday, June 26, 2014
UK Diet and Health Research Awarded £4M
Funding awarded to six projects investigating diet and health to enable the food and drink industry to meet the needs of UK consumers.
Wednesday, June 25, 2014
Scientific News
Shedding Light on HIV Vaccine Design
Broadly speaking - Mathematical modelling of host-pathogen coevolution sheds light on HIV vaccine design.
AACC 2016 Sees Clinical Chemistry Labs Drive Precision Medicine Offerings
Biomarker assays to enable precision medicine and risk assessment, mass spec-based tests designed for use in clinical labs large and small, and liquid biopsy technology captured the spotlight at the AACC annual meeting.
Automated Patch Clamping Trends
Learn more about current practices, preferences and metrics in ion channel drug screening using APC technology.
Lab-on-a-Stick: Miniaturised Clinical Testing For Fast Detection Of Antibiotic Resistance
A portable power-free test for the rapid detection of bacterial resistance to antibiotics has been developed by academics at Loughborough University and the University of Reading.
Genetic Ancestry of Cultivated Strawberry Unravelled
UNH scientists constructed a linkage map of the seven chromosomes of the diploid Fragaria iinumae, which allows them to fill in a piece of the genetic puzzle about the eight sets of chromosomes of the cultivated strawberry.
Progress In Vaccination Against Vespid Venom
Researchers at the Helmholtz Zentrum München and the Technical University Munich have presented a method which facilitates a personalised procedure for wasp allergy sufferers.
New Drug Target for Inflammatory Disorders
Penn study finds enigmatic molecules maintain equilibrium between fighting infection and inflammatory havoc.
Breast Cancer Cells Found To Switch Molecular Characteristics
Spontaneous interconversion between HER2-positive and HER2-negative states could contribute to progression, treatment resistance in breast cancer.
Mechanisms of Calcium Blockers
Researchers describe how the fundamental mode of action of two distinct chemical classes of calcium channel blockers differs.
Some Breast Cancer Patients With Low Genetic Risk Could Skip Chemotherapy
Genetic test can help predict survival and guide treatment options.
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!