New weapon found in the war against superbugs

Behind the Headlines

Thursday June 19 2014

Antibiotic resistance can render previously treatable infections untreatable

Bacteria have evolved resistance to a range of different antibiotics

"British university makes antibiotic resistance breakthrough," The Independent reports after new research found a method that could be used to attack the outer membrane of bacteria. This may help combat the threat of antibiotic resistance.

The study involved a class of bacteria called Gram-negative bacteria, some of which has developed resistance to antibiotics over time.

This is of concern because some Gram-negative bacteria cause serious conditions such as food poisoning (often caused by E.coli and salmonella) and meningitis.

If antibiotic resistance continues to increase, these types of infection could eventually become untreatable using current drugs.

Gram-negative bacteria have an exterior membrane (coating) that protects them from attacks by the human immune system and antibiotic drugs.

Until now little has been known about this defensive barrier, but using the UK's synchrotron facility (think of it as a giant microscope), scientists say they have discovered how it is built.

It may now be possible to find ways to attack the membrane, which would kill the bacteria cells. The advantage of this approach is that by targeting the membranes, rather than the bacteria themselves, there is less chance of resistance evolving.

Although it is early days, this method could eventually lead to the development of new drugs against multi-drug-resistant bacteria.

 

Where did the story come from?

The study was carried out by researchers from the University of East Anglia, the University of St Andrews, Diamond Light Source and the University of Oxford in the UK, and Sichuan Agriculture University, Sichuan University, Wuhan Technical College of Communications and Sun Yat-sen University in China.

There is no information about external funding, although some researchers were supported by the Wellcome Trust and the China Scholarship Council.

The study was published in the peer-reviewed journal Nature.

This story was widely covered in the UK press. Most of the coverage was fair and included useful quotes from the researchers involved, although the tone of the reporting was perhaps more optimistic than is warranted at present.

Some papers also got some basic technical details incorrect; "schoolboy errors" to use an old football cliché (it is the World Cup after all).

For example, the Metro reported that the technique could be used to tackle MRSA. MRSA is in fact a Gram-positive type of bacteria and this study only involved Gram-negative types.

The Daily Telegraph, on the other hand, talked about a "bug responsible for E. coli and salmonella", but although E. coli and salmonella both share the same class, they are entirely different species.

 

What kind of research was this?

This was a laboratory study of the outer membrane of Gram-negative bacteria and the biological processes used to build it. The researchers point out that these bacteria have an outer coating made up of a compound called lipopolysaccharide (LPS).

The building of this protective outer coating depends on several "transport" proteins – which the BBC called "bricklayer" proteins – two of which are called LptD and LptE. These are both crucial to the transport and insertion of LPS, but so far this process has been poorly understood.

The researchers say these two proteins would be a "particularly attractive" target for new drugs, which would not have to enter into the bacteria. However, the development of such drugs is hampered by the lack of a detailed model of the LptD-LptE "complex".

 

What did the research involve?

Researchers were able to map the structure of these proteins for the first time using special X-ray equipment at Diamond Light Source in Oxfordshire, the UK's national synchrotron science facility.

Synchrotrons are a type of particle acceleration, similar to the famous CERN acceleration that was used to detect the Higgs boson. They produce extremely powerful X-rays that help provide detailed images of extremely small objects.

The researchers conducted several experiments to examine the structure of the proteins and the way they work in transporting LPS to the outer membrane.

 

What were the basic results?

The scientists found that the two proteins form a "barrel and plug" structure to transport and insert LPS into the outer surface of the bacteria.

If this process is blocked, the bacteria will become vulnerable to the external environment, as well as the immune system, making them likely to die quickly.

 

How did the researchers interpret the results?

The researchers say their findings help us understand how the outer membrane of Gram-negative bacteria is built.

It may have "significant potential" for the development of novel drugs against multi-drug-resistant bacteria, they say.

 

Conclusion

Antibiotic resistance is already causing thousands of deaths annually and is now considered a major threat, ranking alongside terrorism and climate change.

Gram-negative bacteria such as E. coli, salmonella and Klebsiella are particularly resistant to antibiotics. This study shines a useful light on how such bacteria build a protective outer coating against attack.

It is still early days, but the findings could pave the way for the development of new drugs that attack this process.

As Mark Fielder, professor of medical microbiology at Kingston University, said: "The work reported is at a very early stage, but does offer some potentially useful information in the fight against bacterial resistance.

"What is needed now is the development of a usable inhibitor that can be tested against Gram-negative clinical strains of bacteria to see if there is a longer term value to the research published today."

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

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The 2 comments posted are personal views. Any information they give has not been checked and may not be accurate.

NHS News said on 25 June 2014

Dear Kahn_i - thanks for the headsup
Best Wishes,
The Behind the Headlines Team

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kahn_i said on 24 June 2014

In the conclusion this should read "Gram negative":

"Gram-positive bacteria such as E. coli, salmonella and Klebsiella are particularly resistant to antibiotics. This study shines a useful light on how such bacteria build a protective outer coating against attack."

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Analysis by Bazian

Edited by NHS Choices

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Antibiotics help fight infection caused by bacteria. In this animation the Tokkels learn that antibiotics do not help against viral infections such as cold and flu.

Media last reviewed: 19/07/2014

Next review due: 19/07/2016

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