A novel mechanism of bacteria drug resistance is revealed by discovering a new type of efflux pump in a gram positive microbe. Prof. ZHOU Congzhao and Prof. CHEN Yuxing analyzed the structure of this ABC transporter (Spr0693 and Spr0694-0695) in Streptococcus pneumoniaeat atomic resolution.
The work uncovered a new class of histone forms of gram-positive bacterial ABC transporters, also elucidated the molecular mechanism of drug efflux and provided a structural basis for the design and modification of antibiotics. It was published in Nature Communications on Jan 15, 2018, entitled "Structure of a MacAb-like efflux pump from Streptococcus pneumoniae
Bacteria resist toxic substancesoutside mainly through drug efflux pumps, of which ABC transporter is an important typethat rely on the energy of ATP hydrolysis to discharge toxic substances. In Gram-negative bacteria such as Escherichia coli, an ABC-type drug efflux pump, Macab-TolC, has been found to transport antibiotics from inside the cell to the endometrium, the periplasm and the outer membrane in turn. However, it remains unclear whether similar mechanism exist in Gram-positive bacteria.
Spr0694-0695 and Spr0693were the first MacAb-like drug efflux pump in Gram-positive bacteria. Prof. ZHOU Congzhao and Prof. CHEN Yuxing analyzed the three-dimensional structure of both in Streptococcus pneumoniae using X-ray crystallography. It turned out that Spr0694-0695 is located on the cell membrane unlike the classical ABC transporter; whereas Spr0693 hexamer forms a nanotube-like structure that connects Spr0695 to the cell wall. With integrated biologicalmethods, a substrate transport channel from Spr0695 to Spr0693 wasidentified——an alpha helix between the transmembrane and extracellular regions of Spr0695 controls the opening and closing of the channel withthe energy provided by Spr0694 hydrolyzing ATP.
The work was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the pilot project of the Chinese Academy of Sciences and the basic scientific research fees of the Central Universities of the Ministry of Education.
(Written by GUO JanJan,edited by HUANG DanNing)