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In good hands www.meiko.info TopLine – Reliable hygiene management for dirty utility rooms © Designua / Shutterstock.com INFECTION CONTROL Probably available this autumn Destroying the bacterial defence membrane New test for the early detection of Lyme disease Scientists gain ground against resistance Report: Mark Nicholls The mechanism by which drug- resistant bacteria maintain a defen- sive barrier has been identified by researchers at England’s University of East Anglia (UEA) and their find- ings could result in a new wave of drugs that can bring down those defensive walls rather than attack the bacteria – thus they may not develop drug-resistance at all. Diamond Light Source technology, which generates extremely intense pin-point beams of synchrotron light enables scientists to explore almost any material in atomic detail, and thus to investigate Gram-negative bacteria. The latter are particularly resistant to antibiotics because of the cells’ impermeable lipid-based outer membrane, the barrier that defends against attacks from the human immune system and antibi- otic drugs. It allows the pathogenic bacteria to survive, but the loss of the bar- rier causes them to become more vulnerable and die. Previously the researchers had found an Achilles heel in the defence barrier but how this cell wall is built and maintained – the ‘assembly machinery’ – remained As part of the EU ‘ID Lyme’ pro- ject, the infection immunology working group at the Institute for Hygiene and Applied Immunology at the Centre for Pathophysiology, Infectiology and Immunology at Vienna’s Medical University is work- ing to develop a test to detect Lyme disease (borreliosis) early, thus improving the ability to detect an active infection easier than before, so that healthy people with Lyme disease antibodies in their blood do not receive unnecessary antibi- otic treatment and so that appro- priate treatments can begin early. “Unfortunately, the current standard laboratory test is often unable to detect Lyme disease at an early stage of the infection,” explains Hannes Stockinger, Head of the Institute for Hygiene and Applied Immunology of the Center for Pathophysiology, Infectionology and Immunology of MedUni Vienna. “On top of that, the current test often interprets a mere antibody reaction as an infec- tion and people are treated with antibiotics unnecessarily, because the infection is way in the past or is already completely resolved.” The current test cab only analyse part of the human immune system, namely B-cells but not T-cells, which are needed to fight infection and whose activity indicates infection. The experts are therefore helping to develop the world’s first point-of- care test to detect an active infection so that patients could start appropri- ate treatment. The test, known as the ‘Ixodes Kit’ should be available in the autumn of 2016, said the sci- entists, speaking on the occasion of World Immunology Day 2016. unknown. Lead researcher Professor Changjiang Dong, from UEA’s Norwich Medical School explained: ‘Gram-negative bacteria are among the most difficult to control because they are so resistant to antibiotics. All Gram-negative bacteria have a defensive cell wall. Beta-barrel pro- teins form the gates of the cell wall for importing nutrition and secret- ing important biological molecules.’ The beta-barrel assembly machin- ery (BAM) is responsible for build- ing the gates (beta-barrel proteins) in the cell wall. Dong confirmed that stopping the beta-barrel assembly machine from building the gates in the cell wall would cause the bacte- ria to die. The research - funded by the Wellcome Trust with collabora- tors including Dr Neil Paterson of Diamond Light Source (UK), Dr Phillip Stansfield from the University of Oxford, and Professor Wenjan Wang of Sun Yat-sen University – saw scientists study the gram- negative bacteria E. coli, in which the beta-barrel assembly machinery contains five sub-units, known as BamA, BamB, BamC, BamD and BamE. The researchers wanted to know exactly how these sub-units work together to insert the outer mem- brane proteins into the outer mem- brane or cell wall. Dong: ‘Our research shows the whole beta-barrel assembly machin- ery structures in two states - the starting and finishing states. We found that the five sub-units form a ring structure and work together to perform outer membrane protein insertion using a novel rotation and insertion mechanism… Our work is the first to show the entire BAM complex. It paves the way for devel- oping new-generation drugs. ‘The beta-barrel assembly machin- ery is absolutely essential for Gram- negative bacteria to survive. The sub-unit BamA is located in the outer membrane and exposed to the outer side of the bacteria, which provides a great target for new drugs.’ In human mitochondria, he point- ed out, a similar complex – called sorting and assembly machinery complex (SAM) – is responsible for building the proteins in the outer membrane of mitochondria. The research team also believe that unravelling this mechanism could lead to better understand- ing of human cell dysfunctions linked to disorders such as diabetes, Parkinson’s and other neurodegen- erative diseases. Changjiang Dong is Professor of Molecular Medicine at the University of East Anglia’s Norwich Medical School. His research into antibiotic resistance was named ‘Research Project of the Year’ at the Times Higher Education (THE) Awards 2015. Last year he received a Wellcome Trust Investigator Award for £1.7 million to continue his research. British-based scientists report a breakthrough in combating antibiotic resistance Gram-negative bacteria are among the most difficult to control. 15 www.healthcare-in-europe.com

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