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
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine