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

Ubiquitous Protein Controls Copying of Resistant DNA

Published: Monday, June 09, 2014
Last Updated: Wednesday, June 11, 2014
Bookmark and Share
Researchers have demonstrated how the protein could put antibiotic-resistant bugs in handcuffs.

Staph infections that become resistant to multiple antibiotics don't happen because the bacteria themselves adapt to the drugs, but because of a kind of genetic parasite they carry called a plasmid that helps its host survive the antibiotics.

Plasmids are rings of bare DNA containing a handful of genes that are essentially freeloaders, borrowing most of what they need to live from their bacterial host. The plasmids copy themselves and go along for the ride when the bacteria divide to copy themselves.

A team from Duke and the University of Sydney in Australia has solved the structure of a key protein that drives DNA copying in the plasmids that make staphylococcus bacteria antibiotic-resistant. Knowing how this protein works may now help researchers devise new ways to stop the plasmids from spreading antibiotic resistance in staph by preventing the plasmids from copying themselves.

"If plasmids can't replicate, they go away," said lead author Maria Schumacher, an associate professor of biochemistry in the Duke University School of Medicine. "This is a fantastic new target for antibiotics."

The work appears the week of June 9 in the Proceedings of the National Academy of Sciences.

An essential part of biology, plasmids are so minimalistic they're not even considered alive by themselves. But they're good at ferrying genes from one kind of bacteria to another in a process called horizontal gene transfer. They also excel at adapting to environmental conditions more quickly than their bacterial hosts. Plasmids are able to develop new defenses to an antibiotic and then share that new trick with other bacteria.

Through several years of laborious structural biology to figure out the specific shapes of the molecules involved, the research team has mapped out the structure and function of a protein called RepA, which is crucial to the plasmids' ability to copy its DNA and make a new plasmid.
RepA is a protein that sticks to the beginning of the plasmid's DNA sequence and starts the copying process. "This protein is essential to everything," Schumacher said. "If you don't have it, the plasmid will quickly cease to exist."

Plasmids also need a mechanism to prevent themselves from making too many copies, which would strangle their bacterial host. The researchers have found that RepA is crucial to that function as well.
RepA naturally sticks together in pairs. When a pair of RepA proteins bumps into another pair, as when the cell is starting to get crowded with plasmids, the two pairs of RepA preferentially stick to each other. They form a complex back-to-back, with both having their DNA-grabbing parts facing outward.

When RepA forms this four-part molecule, the plasmids are said to be 'handcuffed,' because two rings of DNA are captured with the locked-up and non-functional RepA complex in the middle.

Once it is handcuffed like this, the plasmid will no longer replicate. Schumacher said this mechanism is apparently how RepA prevents the plasmids from overpopulating the bacterial cell.
Schumacher says RepA is ubiquitous in the plasmid world and doesn't bear much resemblance to other proteins, or to human proteins, making it an attractive drug target. She is hopeful the molecule could be a new site to attack with antibiotics.

"This has been a fun project because we saw many things we didn't expect to see," Schumacher said.

The research was supported by the National Institutes of Health and Department of Energy in the U.S., and the National Health and Medical Research Council of Australia.




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.

Related Content

Breast Cancer Cells Starve for Cystine
Depriving triple negative breast cancer, a treatment-resistant form of breast cancer, of cystine results in cancer cell death.
Wednesday, November 23, 2016
Key Protein for Spinal Cord Repair Identified
Researchers have identifed healing proteins that bridge severed spinal tissue in zebrafish, leading to spinal repair.
Monday, November 07, 2016
New ‘Mega-Complex’ Involved in Cell Signaling Discovered
Duke Health-led researchers have discovered new information about the signaling mechanism of cells that could one day help guide development of more specific drug therapies.
Tuesday, August 09, 2016
Enzyme Structure May Aid Antibiotic Development
Targeted enzyme is essential to every known strain of bacteria.
Wednesday, April 20, 2016
Travelling Salesman Uncorks Synthetic Biology Bottleneck
Computer program scrambles genetic codes for production of repetitive DNA and synthetic molecules.
Thursday, January 07, 2016
Cellular Stress Process Identified in Cardiovascular Disease
Combining the investigative tools of genetics, transcriptomics, epigenetics and metabolomics, a Duke Medicine research team has identified a new molecular pathway involved in heart attacks and death from heart disease.
Tuesday, November 10, 2015
Protein Structures Assemble and Disassemble On Command
Gene sequences may enable control of building bio-structures.
Wednesday, September 23, 2015
Researchers Learn To Measure Aging Process In Young Adults
Biological measures may be combined to determine whether people are aging faster or slower than their peers.
Tuesday, July 07, 2015
Outsmarting HIV With Vaccine Antigens Made to Order
AIDS vaccine researchers may be one step closer to outwitting HIV, thanks to designer antibodies and antigens made to order at Duke University.
Thursday, July 02, 2015
Animals’ Genomic Buffers May Help Humans
Researchers at Duke University School of Medicine and Brigham and Women’s Hospital, Harvard Medical School have identified a mechanism that explains why some mutations can be disease-causing in one genome but benign in another.
Wednesday, July 01, 2015
Tricky Protein May Help HIV Vaccine Development
Researchers have determined the structure of a key part of the HIV envelope protein, the gp41 membrane proximal external region, which previously eluded detailed structural description.
Wednesday, January 15, 2014
Slow-Release "Jelly" Novel Drug Deliverer
Biomedical engineers have developed a novel method to overcome the major hurdles facing a promising new class of peptide drugs to treat diseases such as diabetes and cancer.
Wednesday, January 30, 2013
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.
Largest Resource of Protein-Protein Interactions
Researchers have developed the largest ever database of protein-protein interactions.
Bright Red Fluorescent Protein Created
Scientists have created a bright red, fluorescent protein that could be used to track essential cellular processes.
Protein Self-Regulates Abundance
Researchers have uncovered how a protein, that plays a crucial role in embryonic stem cell renewal, is regulated.
'Lab on the Skin' for Sweat Analysis
Northwestern University researchers develop a low-cost wearable electronic device that collects and analyzes sweat for health monitoring.
Building Better Nanodiscs
Researchers have improved upon the design of nanodiscs that provide an unprecedented view of viral infection.
Breast Cancer Cells Starve for Cystine
Depriving triple negative breast cancer, a treatment-resistant form of breast cancer, of cystine results in cancer cell death.
Novel Urine Test to Predict High-Risk Cervical Cancer
Preliminary studies affirm accuracy and potential cost savings to screen for virus-caused malignancy.
Protein-Folding Gene Helps Heal Wounds
Researchers identified a protein that dramatically accelerates wound healing in animal models.
Crop Yield Gets Boost with Modified Genes
Researchers increase plant proteins that result in more efficient use of sunlight.
Scroll Up
Scroll Down
Skyscraper Banner

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!