A new study led by the scientific director of the Michael G. DeGroote Institute for Infectious Disease Research has uncovered for the first time how bacteria recognize and develop resistance to a powerful antibiotic used to treat superbug infections.
Gerry Wright, a professor in the Department of Biochemistry and Biomedical Sciences at McMaster University in collaboration with colleagues at the John Innes Centre in Norwich, and the University of Cambridge in the UK, have identified the specific mechanism that triggers resistance to vancomycin.
The discovery reveals new understanding about what is happening at the molecular level in vancomycin resistance. It also represents an essential first step in developing new antibiotics that can evade the sensing mechanism of bacteria and overcome resistance.
The research, funded in part by the Canadian Institutes of Health Research and the Canada Research Chairs program, will be published online in the high-impact journal Nature Chemical Biology on April 11, 2010.
"Vancomycin is the antibiotic of last resort and is only given when all other treatments fail," said Wright, who holds the Canada Research Chair in Molecular Studies of Antibiotics and an endowed research Chair in Infection and Anti-Infective Research.
"For years it was thought that resistance would be slow to emerge since vancomycin works in an unusual way. But with the widespread use of the drug to treat infections caused by the hospital superbug MRSA, it has become a serious clinical problem."
MRSA is the short-form for methicillin-resistant staphylococcus aureus, a bacterial infection that is highly resistant to some antibiotics. MRSA bacteria are responsible for a large percentage of hospital-acquired staph infections, but may also be acquired in the community.
Vancomycin is used to treat enterococcal infections that develop in patients following abdominal surgery. Enterococcal bacteria first developed resistance to vancomycin in 1986 and the first case of vancomycin-resistant MRSA (VMRSA) was reported in 2002.
For 20 years, scientists around the world have debated whether bacteria sense the drug itself to trigger resistance or whether they sense the impact it has on the cell wall of bacteria.
Most antibiotics work by inhibiting an enzyme but vancomycin binds to cell wall building blocks, causing a weakness in the structure of the cell wall so the cell bursts and dies.
Some scientists believed that bacteria detect the cell wall degradation to trigger resistance. Others argued that bacteria detect the presence of the drug directly.
Wright and his team studied the vancomycin-resistance mechanism in the harmless soil bacteria Streptomyces coelicolor.
The scientists showed that bacteria detect vancomycin itself. They also conducted preliminary experiments that suggest the same mechanism exists in disease causing bacteria.
"We have finally cracked the alarm system used by bacteria, and hopefully new antibiotics can be developed that don't set it off," said Mark Buttner, a study collaborator and senior scientist at the John Innes Centre.
Marc Ouellette, scientific director of the Institute of Infection and Immunity at the Canadian Institutes for Health Research (CIHR), said the research findings shed new light on the antibiotic resistance issue.
"Thousands of Canadians die every year from antibiotic-resistant infections," Ouellette said. "This issue has long been a priority of the CIHR and this exciting work expands our understanding of how bacteria develop resistance to antibiotics. It lays the groundwork for developing new therapies to prevent and treat antibiotic-resistant infections."
Additional research support was received from the Biotechnology and Biological Sciences Research Council of the UK, the Royal Society and the Medical Research Council (UK).
A photo of Dr. Wright can be downloaded at http://fhs.mcmaster.ca/media/media_20100409.html
For more information, please contact:Gerry Wright, PhD, professor, Department of Biochemistry and Biomedical Sciences at McMaster University
(289) 439-0325 or firstname.lastname@example.orgSusan Emigh, Director, Health Sciences Public Relations, McMaster University
905-525-9140, ext. 22169, email@example.com
Susan Emigh | EurekAlert!
The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft
Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy