Navigation Links
Iowa State, Ames Lab researchers study the structure of drug resistance in tuberculosis
Date:8/22/2012

AMES, Iowa Edward Yu took note of the facts nearly 2 million deaths each year, 9 million infected each year, developments of multidrug-resistant, extensively drug-resistant and now totally drug-resistant strains and decided to shift his research focus to tuberculosis.

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."


'/>"/>
Contact: Edward Yu
ewyu@iastate.edu
515-294-4955
Iowa State University
Source:Eurekalert  

Related biology news :

1. Iowa State, Ames Lab researchers invent new tool to study single biological molecules
2. ORNL researchers improve soil carbon cycling models
3. Researchers identify key culprit causing muscle atrophy
4. Researchers demonstrate control of devastating cassava virus in Africa
5. Researchers pursue red flag for schizophrenia relapse
6. A new line of defense: Researchers find cattle vaccine works to reduce E. coli O157:H7
7. Wayne State researchers working to improve genetic analysis, disorder detection
8. Superbird stuns researchers
9. Massachusetts Eye and Ear researchers discover elusive gene that causes a form of blindness from birth
10. Researchers monitor red tides in Chesapeake Bay
11. BUSM researchers find link between childhood abuse and age at menarche
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Iowa State, Ames Lab researchers study the structure of drug resistance in tuberculosis
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 /PRNewswire/ ... product subsidiary of Infosys (NYSE: INFY ), and ... global partnership that will provide end customers with ... banking and payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ... area for financial services, but it also plays a fundamental ...
(Date:4/26/2016)... , April 27, 2016 ... the  "Global Multi-modal Biometrics Market 2016-2020"  report to ... ) , The analysts forecast the ... CAGR of 15.49% during the period 2016-2020.  ... number of sectors such as the healthcare, BFSI, ...
(Date:4/15/2016)... 2016 Research and Markets has ... Market 2016-2020,"  report to their offering.  , ... ,The global gait biometrics market is expected to ... period 2016-2020. Gait analysis generates multiple ... used to compute factors that are not or ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... 27, 2016 /PRNewswire/ - BIOREM Inc. (TSX-V: BRM) ("Biorem" or ... its major shareholders, Clean Technology Fund I, LP and ... based venture capital funds which together hold ... a fully diluted, as converted basis), that they have ... entire equity holdings in Biorem to TUS Holdings Co. ...
(Date:6/27/2016)... ... ... Parallel 6 , the leading software as a service (SaaS) provider ... Patient Encounter CONSULT module which enables both audio and video telemedicine communication between the ... the CONSULT module, patients and physicians can schedule a face to face virtual patient ...
(Date:6/27/2016)... 27, 2016  Liquid Biotech USA ... of a Sponsored Research Agreement with The University ... (CTCs) from cancer patients.  The funding will be ... correlate with clinical outcomes in cancer patients undergoing ... then be employed to support the design of ...
(Date:6/24/2016)... 24, 2016 Epic Sciences unveiled a ... susceptible to PARP inhibitors by targeting homologous recombination ... The new test has already been incorporated into ... cancer types. Over 230 clinical trials ... pathways, including PARP, ATM, ATR, DNA-PK and WEE-1. ...
Breaking Biology Technology: