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

   
   

   Promising agents burst through 'superbug' defenses to fight antibiotic resistance

2. Date:

   April 9, 2014

   Source:

   American Chemical Society

   Summary:

   In the fight against 'superbugs,' scientists have discovered a class of agents that can make some of the most notorious strains vulnerable to the same antibiotics that they once handily shrugged off. The report on the promising agents called metallopolymers -- large, metal-containing molecules -- demonstrated that they evaded the bacteria's defensive enzymes and destroyed its protective walls, causing the bacteria to burst.
   
   

   In the fight against "superbugs," scientists have discovered a class of agents that can make some of the most notorious strains vulnerable to the same antibiotics that they once handily shrugged off. The report on the promising agents called metallopolymers appears in the Journal of the American Chemical Society.

   Chuanbing Tang and colleagues note that the antibiotic-resistant bacteria known as MRSA (methicillin-resistant Staphylococcus aureus) is responsible for a significant fraction of the infections that patients acquire in hospitals. According to the Centers for Disease Control and Prevention, MRSA usually spreads in hospitals when a health care provider with contaminated hands unknowingly passes it along to a patient. It can cause serious problems such as pneumonia, and can lead to death. One of the ways MRSA undermines conventional treatments is by producing enzymes that inactivate traditional antibiotics such as penicillin. Scientists have been developing new agents to combat these enzymes, but the agents so far have fallen short. Tang's team wanted to find a better alternative.

   They tested a recently discovered class of metallopolymers -- large, metal-containing molecules -- against several strains of MRSA. When paired with the same antibiotics MRSA normally dispatches with ease, the polymer/antibiotic combo evaded the bacteria's defensive enzymes and destroyed its protective walls, causing the bacteria to burst. Also, the metallopolymers mostly left red blood cells alone, which suggests they might have minimal side effects. "These discoveries could pave a new platform to design antibiotics and antimicrobial agents to battle multidrug-resistant bacteria and superbugs," the researchers state.

   Story Source:

   The above story is based on materials provided by American Chemical Society.Note: Materials may be edited for content and length.

   Journal Reference:

   1. Jiuyang Zhang, Yung Pin Chen, Kristen P. Miller, Mitra S. Ganewatta, Marpe Bam, Yi Yan, Mitzi Nagarkatti, Alan W. Decho, Chuanbing Tang. Antimicrobial Metallopolymers and Their Bioconjugates with Conventional Antibiotics against Multidrug-Resistant Bacteria. Journal of the American Chemical Society, 2014; 136 (13): 4873 DOI: 10.1021/ja5011338