Navigation Links
Protein could put antibiotic-resistant bugs in handcuffs
Date:6/9/2014

DURHAM, N.C. -- 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.


'/>"/>

Contact: Karl Leif Bates
karl.bates@duke.edu
919-681-8054
Duke University
Source:Eurekalert  

Related biology news :

1. Jekyll and Hyde protein linked to type 1 diabetes
2. Faster, higher, stronger: A protein that enables powerful initial immune response
3. Specific protein may help beta cells survive in type 1 diabetes
4. Design of self-assembling protein nanomachines starts to click
5. Subtle change in DNA, protein levels determines blond or brunette tresses, study finds
6. Sneaky bacteria change key proteins shape to escape detection
7. Quantity, not quality: Risk of sudden cardiac death tied to protein overproduction
8. Does apolipoprotein E mimetic peptide reduce neuronal apoptosis induced by DBI?
9. Protein sharpens salmonella needle for attack
10. Protein Data Bank: 100,000 structures
11. New technique tracks proteins in single HIV particle
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Protein could put antibiotic-resistant bugs in handcuffs
(Date:2/2/2017)... YORK , Feb. 2, 2017  EyeLock LLC, ... released a new white paper " What You Should ... The problem of ensuring user authenticity is a growing ... the authentication of users. However, traditional authentication schemes such ... Biometric authentication offers an elegant solution ...
(Date:1/26/2017)... -- Crossmatch, a leading provider of security and identity management ... fraud, waste and abuse in assistance operations around the ... Disaster Relief conference in Panama City ... foreign assistance organizations throughout Latin America ... largely unacknowledged problem in the foreign assistance and disaster ...
(Date:1/23/2017)... Jan. 23, 2017  The latest mobile market research ... have dropped dramatically. The quarterly average price of a ... $276 in Q4 2016.  There are now 120 sub-$150 ... $116, up from just 28 a year ago at ... to Maxine Most , Acuity Market Intelligence Principal, ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... ... ... Chef Jodi Abel has returned from her three-week tour through the ... a number of delicious recipes and new techniques to share with her Lajollacooks4u guests. ... province. It is internationally renowned for its incredible wine farms, beautiful environment, boutiques ...
(Date:2/24/2017)... , Feb. 24, 2017  Driven by consumers, ... are now the fastest growing categories, finds the ... Actives in Personal Care: Multi-regional Market Analysis and ... management consulting firm Kline. "Biotechnology actives ... make them more effective for skin and hair ...
(Date:2/24/2017)... Pa., Feb. 24, 2017  VWR Corporation (NASDAQ: VWR), the ... laboratory and production customers, today reported its financial results for ... Highlights: 4Q16 record quarterly ... 1.0% on an organic basis. ... an organic basis, while the Americas net sales increased 2.5%, ...
(Date:2/23/2017)... ... February 23, 2017 , ... BellBrook Labs ... to include an array of biochemical analyses critical for Lead Discovery. The ... hit-to-lead and SAR programs, including inhibitor potency and selectivity, mechanism of action, and ...
Breaking Biology Technology: