China University of Science and Technology found a new type of Gram-positive drug efflux pump

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The National Research Center of Hefei Microscale Physical Science and the School of Life Sciences of the University of Science and Technology of China, Professor Zhou Congzhao and Professor Chen Yuxing, analyzed a novel ABC transporter (Spr0693 and Spr0694) in Streptococcus pneumoniae. The atomic resolution structure of -0695) reveals a new mechanism of resistance to Gram-positive bacteria. The research was published on “Nature Communications” on January 15, 2018 under the title “Structure of a MacAB-like efflux pump from Streptococcus pneumoniae”.

China University of Science and Technology found a new type of Gram-positive bacteria Drug efflux pump

The drug efflux pump is the main way for bacteria to resist external toxic substances, and ABC transporter is an important type of drug efflux pump, which relies on The energy of ATP hydrolysis releases these toxic substances. An ABC-type drug efflux pump, MacAB-TolC, has been found in Gram-negative bacteria such as Escherichia coli, which can transport antibiotics from the intracellular, intraperitoneal, and outer membranes to the outside of the bacteria. However, it is unclear whether a similar system is present in Gram-positive bacteria.

Professor Zhou Congzhao and Professor Chen Yuxing used X-ray crystallography to analyze the three-dimensional structure of ABC transporters Spr0694-0695 and Spr0693 in Streptococcus pneumoniae, which was the first Gram-positive bacteria in MacAB. -like drug efflux pump. Spr0694-0695 is located on the cell membrane, unlike the classical ABC transporter, which has 8 transmembrane helices and a larger extracellular domain; whereas Spr0693 hexamers form a nanotubular structure that links Spr0695 to the cell wall. Integrating experimental methods of structural biology, biochemistry and microbial genetics, identified a substrate transport channel from Spr0695 to Spr0693, and found that an alpha helix between the transmembrane and extracellular regions of Spr0695 controls the switch of the channel. The energy required for the transport process is provided by Spr0694 hydrolyzed ATP. This work not only discovered the tissue form of a new class of Gram-positive bacteria ABC transporter, but also clarified the molecular mechanism of drug efflux, providing a structural basis for the design and transformation of antibiotics.

Professor Zhou Congzhao, Prof. Chen Yuxing and Associate Professor Jiang Yongliang of China University of Science and Technology are co-authors of the paper. Dr. Yang Hongbo, a Ph.D. student at China University of Science and Technology, Hou Wenzhao, a special associate researcher, and Cheng Mengting, a doctoral student, are the co-first authors of the paper. Crystal diffraction data collection was done in Shanghai light source.

The work was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences Pilot Project, and the Basic Research Business Fee of the Central University of Education.

Article link:https://www.nature.com/articles/s41467-017-02741-4

(News: China University of Science and Technology News Net)