(Press-News.org) Contact information: Stewart Cole
stewart.cole@epfl.ch
41-216-931-851
Ecole Polytechnique Fédérale de Lausanne
Tuberculosis: Nature has a double-duty antibiotic up her sleeve
A natural antibiotic turns out to be a lethal weapon in the fight against tuberculosis. Scientists have discovered it has an unexpected dual action that dramatically reduces the probability that TB bacteria will become resistant
Technology has made it possible to synthesize increasingly targeted drugs. But scientists still have much to learn from Mother Nature. Pyridomycin, a substance produced by non-pathogenic soil bacteria, has been found to be a potent antibiotic against a related strain of bacteria that cause tuberculosis. The EPFL scientists who discovered this unexpected property now have a better understanding of how the molecule functions. Its complex three-dimensional structure allows it to act simultaneously on two parts of a key enzyme in the tuberculosis bacillus, and in doing so, dramatically reduce the risk that the bacteria will develop multiple resistances. The researchers, along with their colleagues at ETH Zurich, have published their results in the journal Nature Chemical Biology.
Stewart Cole, director of EPFL's Global Health Institute, led a team that discovered the anti-tuberculosis effect of pyridomycin in 2012. By inhibiting the action of the "InhA" enzyme, pyridomycin literally caused the thick lipid membrane of the bacterium to burst. Now the scientists understand how the molecule does this job.
Dual anti-mutation ability
The tuberculosis bacillus needs the InhA enzyme along with what scientists refer to as a "co-factor," which activates the enzyme, in order to manufacture its membrane. The scientists discovered that pyridomycin binds with the co-factor, neutralizing it.
But pyridomycin doesn't stop there. It also blocks another element needed for making the membrane, the InhA binding site. "Researchers in the pharmaceutical industry have been looking for this weakness in the TB bacillus for decades," explains Ruben Hartkoorn, first author on the article.
By binding simultaneously onto these two elements and neutralizing them, pyridomycin prevents the bacterium from generating its membrane, and it ends up bursting like a balloon. Better still, this dual action drastically reduces the risk that the bacteria will become resistant, because in order to develop resistance, two different specific mutations must exist at the same time. This is increasingly important because cases of multi-resistant TB are on the rise.
Nature's twisting paths – a lesson in efficiency
"It's a powerful lesson from nature with respect to drug design," explains Cole, co-author and EPFL professor. "The three-dimensional structures of naturally occurring molecules are often more complex, more twisted, than synthetic molecules, and that's precisely what allows pyridomycin to bind onto these two sites simultaneously."
In fact, it binds so effectively that the molecule is not yet ready to be used therapeutically: it doesn't last long enough in the patient's body. This is the point at which bioengineering needs to take over from Mother Nature – to develop a more robust version of the molecule. This is what the ETH team led by Karl-Heinz Altmann is working on. "Eventually we could multiply the molecule's binding sites, so that it could inhibit critical functions of other pathogenic bacteria," says Cole.
### END
Tuberculosis: Nature has a double-duty antibiotic up her sleeve
A natural antibiotic turns out to be a lethal weapon in the fight against tuberculosis. Scientists have discovered it has an unexpected dual action that dramatically reduces the probability that TB bacteria will become resistant
2013-12-03
ELSE PRESS RELEASES FROM THIS DATE:
New research will allow more reliable dating of major past events
2013-12-03
New research will allow more reliable dating of major past events
Academics have developed a new internationally agreed radiocarbon calibration curve which will allow key past events to be dated more accurately
Academics have developed a new method ...
LSTM researchers among first to sequence snake genome
2013-12-03
LSTM researchers among first to sequence snake genome
Researchers sequence genome for the king cobra
Researchers from LSTM, along with a team of international biologists who have recently sequenced the genome of the king cobra, say that their work reveals ...
Have researchers found a new treatment for sepsis?
2013-12-03
Have researchers found a new treatment for sepsis?
University of Leicester academics discover new receptor that may be instrumental in the body's response to devastating disease
Sepsis, or septicaemia, is a devastating disease that is difficult to diagnose early ...
Talk therapy may reverse biological changes in PTSD patients
2013-12-03
Talk therapy may reverse biological changes in PTSD patients
A study of biological markers of PTSD in Biological Psychiatry
Philadelphia, PA, December 3, 2013 – A new paper published in Biological Psychiatry suggests that cognitive behavioral therapy for posttraumatic ...
Citrus fruit inspires a new energy-absorbing metal structure
2013-12-03
Citrus fruit inspires a new energy-absorbing metal structure
Researchers use a naturally occurring structure to design aluminum materials
It has been said that nature provides us with everything that we need. A new study appearing in Springer's Journal of Materials Science ...
Researchers turn current sound-localization theories 'on their ear'
2013-12-03
Researchers turn current sound-localization theories 'on their ear'
Mass. Eye and Ear scientists challenge the two dominant theories of how people localize sounds
BOSTON (Dec. 3, 2013) – The ability to localize the source of sound is important for navigating ...
New thermoelectronic generator
2013-12-03
New thermoelectronic generator
Highly efficient new design, described in 'Journal of Renewable and Sustainable Energy,' converts heat and solar energy into electricity
WASHINGTON D.C. Dec. 3, 2013 -- Through a process known as thermionic conversion, heat ...
UK review examines gender differences in COPD patients
2013-12-03
UK review examines gender differences in COPD patients
LEXINGTON, Ky. (Dec. 3, 2013) — A new study review authored by the University of Kentucky's Dr. David Mannino examines the gender differences in the prevalence, pathophysiology, and clinical presentation of ...
Unlikely collaboration leads to discovery of 'gender-bending' plant
2013-12-03
Unlikely collaboration leads to discovery of 'gender-bending' plant
Bucknell professor Chris Martine never expected to be working with his mentor on identifying a new wild eggplant in Australia, especially since Martine's former colleague passed away years ago
Bucknell ...
Neurofeedback tunes key brain networks, improving subjective well-being in PTSD
2013-12-03
Neurofeedback tunes key brain networks, improving subjective well-being in PTSD
Pioneering research conducted at Western University (London, Canada) points to a promising avenue for the treatment of post-traumatic stress disorder (PTSD): utilising neurofeedback ...
LAST 30 PRESS RELEASES:
Global cervical cancer vaccine roll-out shows it to be very effective in reducing cervical cancer and other HPV-related disease, but huge variations between countries in coverage
Negativity about vaccines surged on Twitter after COVID-19 jabs become available
Global measles cases almost double in a year
Lower dose of mpox vaccine is safe and generates six-week antibody response equivalent to standard regimen
Personalised “cocktails” of antibiotics, probiotics and prebiotics hold great promise in treating a common form of irritable bowel syndrome, pilot study finds
Experts developing immune-enhancing therapies to target tuberculosis
Making transfusion-transmitted malaria in Europe a thing of the past
Experts developing way to harness Nobel Prize winning CRISPR technology to deal with antimicrobial resistance (AMR)
CRISPR is promising to tackle antimicrobial resistance, but remember bacteria can fight back
Ancient Maya blessed their ballcourts
Curran named Fellow of SAE, ASME
Computer scientists unveil novel attacks on cybersecurity
Florida International University graduate student selected for inaugural IDEA2 public policy fellowship
Gene linked to epilepsy, autism decoded in new study
OHSU study finds big jump in addiction treatment at community health clinics
Location, location, location
Getting dynamic information from static snapshots
Food insecurity is significant among inhabitants of the region affected by the Belo Monte dam in Brazil
The Society of Thoracic Surgeons launches new valve surgery risk calculators
Component of keto diet plus immunotherapy may reduce prostate cancer
New circuit boards can be repeatedly recycled
Blood test finds knee osteoarthritis up to eight years before it appears on x-rays
April research news from the Ecological Society of America
Antimicrobial resistance crisis: “Antibiotics are not magic bullets”
Florida dolphin found with highly pathogenic avian flu: Report
Barcodes expand range of high-resolution sensor
DOE Under Secretary for Science and Innovation visits Jefferson Lab
Research expo highlights student and faculty creativity
Imaging technique shows new details of peptide structures
MD Anderson and RUSH unveil RUSH MD Anderson Cancer Center
[Press-News.org] Tuberculosis: Nature has a double-duty antibiotic up her sleeveA natural antibiotic turns out to be a lethal weapon in the fight against tuberculosis. Scientists have discovered it has an unexpected dual action that dramatically reduces the probability that TB bacteria will become resistant