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.
Edward Yu/Iowa State University.
This ribbon diagram shows the crystal structure of the Rv3066 regulator that controls the expression of a pump that removes toxins from tuberculosis bacteria.
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.”
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.”
Mike Krapfl | Newswise Science News
Further reports about: > Advanced Investigator Grant > Advanced Photon Source > Ames > Argonne > Energy Science > Iowa > Laboratory > M. tuberculosis > Photon > Photon Source > Source > Tuberculosis > Veterinary Public Health > X-ray beam > X-ray microscopy > doctoral research > drug resistance > environmental change > molecular mechanism > protein structures > resistance > specimen processing
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News