Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New advance to combat antibiotic-resistant pneumonia and malaria

21.01.2004


Yeast used as surrogate model



New biochemical studies may hold clues to more powerful malaria and pneumonia treatments that could save more than 2 million lives worldwide. Using baker’s yeast as a surrogate disease model, researchers led by Dartmouth Medical School are exploring why enzymes in organisms that cause pneumonia and malaria are becoming increasingly resistant to antibiotics. This work could provide the answer to testing a new generation of drugs to combat these prevalent diseases.

Investigators used genetically modified yeast enzymes to pinpoint the mutations responsible for the antibiotic resistance of Pneumocystis jirovecii, which causes a type of pneumonia that is the most serious and prevalent AIDS-associated opportunistic infection and a threat to other immunocompromised patients, such as those undergoing therapy for cancer and organ transplantation. Pneumonia was responsible for more than 61,000 deaths in the US in 2001, according to the National Center for Health Statistics.


Appearing in the January 23 Journal of Biological Chemistry, the study examines the mutations responsible for disease’s tolerance toward atovaquone (ATV), a drug prescribed since 1995 that inhibits a respiratory enzyme called the cytochrome bc1 complex, that is essential for the pathogen’s survival. The lead author, Dr. Jacques Kessl, a research associate in biochemistry at DMS, said the study addresses recent evidence that indicates that pathogens that cause malaria and pneumonia are increasing resistance to ATV by developing mutations that prevent the drug from acting on the bc1 complex.

"We were able to isolate the genetic mutations that enable the pathogens to resist the drug when it is introduced to our yeast samples," said Dr. Bernard Trumpower, professor of biochemistry at DMS and corresponding author of the study. "As the genetically modified yeast strains now display atovaquone resistance identical to that found in pneumocystis, these yeast can be used to design new drugs to make the appearance of resistance more unlikely."

The study builds on prior research in Trumpower’s lab that used yeast enzymes as accurate and easily modified models to explore the resistance to ATV. It is not possible to grow pneumocystis enzymes in the large quantities necessary to isolate and study the cytochrome bc1 complex. Yeast is an excellent resource that can be manufactured in large quantities and can be easily modified to take on the qualities of more dangerous pathogens.

The researchers were able to genetically transfer into the yeast cytochrome b mutations like those found in the atovaquone resistant pneumocystis and found that these mutations caused the yeast to acquire similar resistance to ATV. Additionally, the team used a computer program to construct molecular models of the enzymes. "We can now visualize the different mutations in three dimensions to predict how the enzyme will react to different changes, like the introduction of a new antibiotic," said co-author Benjamin Lange, a research assistant at DMS.

"We are infinitely further along than we were three years ago in terms of understanding the basis for resistance in these organisms," said Trumpower. The co-authors of the study are Dr. Steven Meshnick from the University of North Carolina and Dr. Brigitte Meunier from the Wolfson Institute for Biomedical Research in London. The study was funded in part by the NIH.

Andy Nordhoff | EurekAlert!
Further information:
http://www.dartmouth.edu/

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>