Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Studying the Structure of Drug Resistance in TB

Published: Wednesday, August 29, 2012
Last Updated: Wednesday, August 29, 2012
Bookmark and Share
Researchers at Iowa State and Ames Laboratory have used X-ray crystallography to study the structure of the tuberculosis efflux pump regulator.

Edward Yu, an Iowa State University and Ames Laboratory researcher, has described in the journal Nature the three-part structure that allows E. coli bacteria to pump out toxins and resist antibiotics.

And now, in a paper published online by the journal Nucleic Acids Research, a research team led by Yu describes the structure of a regulator that controls the expression of the multidrug efflux pump in Mycobacterium tuberculosis.

Yu – a professor of physics and astronomy, of chemistry, of biochemistry, biophysics and molecular biology in Iowa State’s College of Liberal Arts and Sciences and an associate of the U.S. Department of Energy's Ames Laboratory – said the latest study is a starting point for a better understanding of how the tuberculosis bacterium is able to resist drugs.

The development of strains totally resistant to drugs “inspired us to move in this direction and try to understand the mechanism in developing drug resistance,” Yu said.

“It is obvious that the emergence of these drug-resistant TB strains has evolved into a major threat and challenges our global prospects for TB control,” Yu’s research team wrote in its latest paper. “Thus, knowledge of the molecular mechanisms underlying drug resistance in M. tuberculosis is essential for the development of new strategies to combat this disease.”

Yu’s research is currently supported by the National Institutes of Health. The researchers’ use of the Advanced Photon Source at Argonne National Laboratory in Argonne, Ill., was supported by the U.S. Department of Energy’s Office of Basic Energy Sciences.

In addition to Yu, the research team includes Qijing Zhang, Iowa State’s Frank Ramsey Endowed Professor of Veterinary Microbiology and Preventive Medicine and the College of Veterinary Medicine’s officer of graduate education; Kanagalaghatta Rajashankar, a senior research associate in chemistry and chemical biology at Cornell University in Ithaca, N.Y., and associate director of the Northeastern Collaborative Access Team facility at the Advanced Photon Source; Iowa State post-doctoral research associates and Ames Lab associates Feng Long and Chih-Chia Su; Iowa State post-doctoral research associate Lei Dai; Iowa State graduate students and Ames Lab student associates Jani Reddy Bolla, Sylvia Do and Hsiang-Ting Lei; recent Iowa State graduate Xiao Chen; and Ames Lab undergraduate summer interns Jillian Gerkey and Daniel Murphy.

Prior to Yu’s study, not much was known about the structure and function of the tuberculosis efflux pump regulator known as Rv3066.

That, in part, is because researchers have attributed drug resistance in tuberculosis to the bacterium’s very thick cell wall. That wall makes it very difficult to get drugs into the bacterium.
The researchers used X-ray crystallography (including X-ray beams produced by the Advanced Photon Source) to study the Rv3066 structure. They collected data showing the regulator when the toxic compound ethidium bromide was present and when it was not.

The data revealed an asymmetric, two-part molecule with a spiral structure. The structure is flexible, allowing the regulator to recognize and respond to multiple drugs. In the presence of ethidium, Yu’s group says the regulator responds with a rotational motion, inducing expression of the efflux pump that rids the bacterium of antimicrobial drugs.

Studying that structure and mechanism could make a difference in the fight against drug-resistant tuberculosis: “Elucidating the regulatory systems of multidrug efflux pumps in M. tuberculosis,” Yu and the researchers wrote in their paper, “should allow us to understand how this bacterium contributes to multidrug resistance and how it adapts to environmental changes.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Using Forensic Technology to Track Down Drug Residues in Milk
Veterinarians at Iowa State University are using advanced forensic techniques and the same technology used by crime scene investigators to monitor drug residues in milk and meat.
Tuesday, July 01, 2014
OnLine Seed Technology and Business Graduate Program
The Graduate Program in Seed Technology and Business (STB) provides a unique opportunity for seed professionals to grow through the understanding of both science and technology that is key to seed industry, and broadly applicable business subjects.
Monday, November 09, 2009
Iowa State University Researcher Develops Software that Sidesteps Effects of qPCR-Inhibitory Materials
The software system PREXCEL-Q can provide a way to detect and avoid inhibition, and enables investigators to consistently design qPCR reactions.
Wednesday, March 21, 2007
Scientific News
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
Playing 'Tag' with Pollution lets Scientists See Who's It
Using a climate model that can tag sources of soot from different global regions and can track where it lands on the Tibetan Plateau, researchers have determined which areas around the plateau contribute the most soot — and where.
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
First Artificial Ribosome Designed
Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell.
High-Resolution 3D Images Reveal the Muscle Mitochondrial Power Grid
NIH mouse study overturns scientific ideas on energy distribution in muscle.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
Paving the way to Better Ovarian Cancer Diagnosis
Aïcha BenTaieb will present her invention for automated identification of ovarian cancer’s many subtypes at an international conference this fall.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!