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Achilles' heel in antibiotic-resistant bacteria discovered

Date:
June 18, 2014
Source:
University of East Anglia
Summary:
A breakthrough in the race to solve antibiotic resistance has been made by scientists. New research reveals an Achilles' heel in the defensive barrier that surrounds drug-resistant bacterial cells. The findings pave the way for a new wave of drugs that kill superbugs by bringing down their defensive walls rather than attacking the bacteria itself. It means that in future, bacteria may not develop drug-resistance at all.

Researchers investigated Gram-negative bacteria, which cause a vast range of infections, including e-coli, salmonella, gonorrhea, pseudomonas, and meningitis. The outer surface of a Gram-negative bacterial cell acts as a disguising “cloak” that provides a barrier against toxic compounds such as antibiotics and camouflages the invading organism to evade detection and destruction by the body’s defences. Using the intense light produced by Diamond Light Source, the UK's national synchotron science facility, to study these bacteria at an atomic level, the researchers were able to pinpoint the structure of the integral protein responsible for the final stage of creating the bacteria’s camouflage.
Credit: Diamond Light Source 2014

New research published today in the journal Nature reveals an Achilles' heel in the defensive barrier which surrounds drug-resistant bacterial cells.

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The findings pave the way for a new wave of drugs that kill superbugs by bringing down their defensive walls rather than attacking the bacteria itself. It means that in future, bacteria may not develop drug-resistance at all.

The discovery doesn't come a moment too soon. The World Health Organization has warned that antibiotic-resistance in bacteria is spreading globally, causing severe consequences. And even common infections which have been treatable for decades can once again kill.

Researchers investigated a class of bacteria called 'Gram-negative bacteria' which is particularly resistant to antibiotics because of its cells' impermeable lipid-based outer membrane.

This outer membrane acts as a defensive barrier against attacks from the human immune system and antibiotic drugs. It allows the pathogenic bacteria to survive, but removing this barrier causes the bacteria to become more vulnerable and die.

Until now little has been known about exactly how the defensive barrier is built. The new findings reveal how bacterial cells transport the barrier building blocks (called lipopolysaccharides) to the outer surface.

Group leader Prof Changjiang Dong, from UEA's Norwich Medical School, said: "We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface. Importantly, we have demonstrated that the bacteria would die if the gate is locked."

"This is really important because drug-resistant bacteria is a global health problem. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each year.

"The number of super-bugs are increasing at an unexpected rate. This research provides the platform for urgently-needed new generation drugs."

Lead author PhD student Haohao Dong said: "The really exciting thing about this research is that new drugs will specifically target the protective barrier around the bacteria, rather than the bacteria itself.

"Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future."

This research was funded by Wellcome Trust. Research collaborators included the University of St Andrews, Dr Neil Paterson of Diamond Light Source (UK), Dr Phillip Stansfield from the University of Oxford, and Prof Wenjan Wang of Sun Yat-sen University (China).


Story Source:

The above story is based on materials provided by University of East Anglia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Haohao Dong, Quanju Xiang, Yinghong Gu, Zhongshan Wang, Neil G. Paterson, Phillip J. Stansfeld, Chuan He, Yizheng Zhang, Wenjian Wang, Changjiang Dong. Structural basis for outer membrane lipopolysaccharide insertion. Nature, 2014; DOI: 10.1038/nature13464

Cite This Page:

University of East Anglia. "Achilles' heel in antibiotic-resistant bacteria discovered." ScienceDaily. ScienceDaily, 18 June 2014. <www.sciencedaily.com/releases/2014/06/140618140014.htm>.
University of East Anglia. (2014, June 18). Achilles' heel in antibiotic-resistant bacteria discovered. ScienceDaily. Retrieved March 5, 2015 from www.sciencedaily.com/releases/2014/06/140618140014.htm
University of East Anglia. "Achilles' heel in antibiotic-resistant bacteria discovered." ScienceDaily. www.sciencedaily.com/releases/2014/06/140618140014.htm (accessed March 5, 2015).

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