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:4/13/2017)... , April 13, 2017 According to a new ... Authentication, Identity Analytics, Identity Administration, and Authorization), Service, Authentication Type, Deployment Mode, ... IAM Market is expected to grow from USD 14.30 Billion in 2017 ... (CAGR) of 17.3%. ... MarketsandMarkets Logo ...
(Date:4/11/2017)... Research and Markets has announced the addition of the "Global ... ... at a CAGR of 30.37% during the period 2017-2021. ... based on an in-depth market analysis with inputs from industry experts. ... the coming years. The report also includes a discussion of the ...
(Date:4/11/2017)... 11, 2017 NXT-ID, Inc. (NASDAQ:   ... announces the appointment of independent Directors Mr. Robin D. ... Board of Directors, furthering the company,s corporate governance and expertise. ... Gino Pereira , ... forward to their guidance and benefiting from their considerable expertise ...
Breaking Biology News(10 mins):
(Date:4/21/2017)... ... April 21, 2017 , ... The 2017 Colorado Manufacturing Awards ... 30 nominees and well as the first-year award for 2017 Manufacturing Women of ... was hosted by CompanyWeek and Manufacturers Edge, among other sponsors. , The ...
(Date:4/21/2017)... ... 21, 2017 , ... Frederick Innovative Technology Center, Inc. (FITCI), ... and technology start-ups, is hosting “Celebration Friday” (a festive gathering highlighting client success ... libations and networking at 3:30 p.m. at FITCI’s 4539 Metropolitan Court location, off ...
(Date:4/20/2017)... SANTA BARBARA, CALIFORNIA (PRWEB) , ... April 20, 2017 , ... ... process optimization firm for the life sciences and healthcare industries, is pleased to announce ... of the new established USDM subsidiary “USDM Europe GmbH” based in Germany. , ...
(Date:4/20/2017)... ... 20, 2017 , ... Parallel6™ , the leader in mClinical™ technologies for ... were named one of the 2017 Top 10 eClinical Trial Management Solution Providers ... industry. , “We take pride in honoring Parallel6 as one of the top 10 ...
Breaking Biology Technology: