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:3/21/2016)... March 22, 2016 Unique ... passcodes for superior security   ... provider of secure digital communications services, today announced it ... and offer enterprise customers, particularly those in the Financial ... and voice authentication within a mobile app, alongside, and ...
(Date:3/15/2016)... March 15, 2016 Yissum Research Development ... technology-transfer company of the Hebrew University, announced today the ... sensing technology of various human biological indicators. Neteera Technologies ... million from private investors. ... the detection of electromagnetic emissions from sweat ducts, enables ...
(Date:3/11/2016)... March 11, 2016 --> ... research report "Image Recognition Market by Technology (Pattern Recognition), ... Advertising), by Deployment Type (On-Premises and Cloud), by Industry ... published by MarketsandMarkets, the global market is expected to ... 29.98 Billion by 2020, at a CAGR of 19.1%. ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... ... 2016 , ... Founder of the Fitzmaurice Hand Institute in ... of the hand by the National Board of Physicians and Surgeons, as of ... in his pursuit of providing the most comprehensive, effective treatment for his patients, ...
(Date:5/25/2016)... SALT LAKE CITY, UTAH. (PRWEB) , ... May 25, 2016 , ... ... create efficiencies in healthcare information exchange, today announced that Charles W. Stellar has been ... served as WEDI’s interim CEO since January 2016. As an executive leader with more ...
(Date:5/24/2016)... (PRWEB) , ... May 24, 2016 , ... ... attacks, diabetes, and traumatic injuries, will be accelerated by research at Worcester Polytechnic ... into engines of wound healing and tissue regeneration. , The novel method, developed ...
(Date:5/24/2016)... ... May 24, 2016 , ... Media Cybernetics, global image analysis ... corporate branding reflects a results-driven revitalization for a company with a renewed focus ... include a crisp, refreshed logo and a new web presence. , “I believe ...
Breaking Biology Technology: