Every coin has two sides. When people are infected with bacteria and suggested by doctors to take various drugs, they are worried about whether the drug resistance would come into being?

Many bacteria pathogens have gained resistance to multiple types of antibiotics. As the biggest threat to the public health all over the world, bacteria drug resistance has grown to be a hot issue of common interest to WHO and governments worldwide.

According to the previous findings, bacteria use various tactics to resist the toxic effects of antibiotics. One simple and effective way is to pump drugs out of the cells using membrane-located transporters, which is similar to what cancer cells do to resist chemotherapy.

In a study published in Cell Research, Prof. ZHANG Kai’s group and Prof. ZHAO Yongfang’s group released their structural and functional studies on a multidrug transporter from E. coli.

MdfA belongs to the largest secondary active transporter family, major facilitator superfamily (MFS). The crystal structure of MdfA-chloramphenicol complex at 2.4 Å resolution represents the first reported structure of an MFS multidrug transporter complexed with its substrate drug. MdfA forms 12 transmembrane helical topology structures, which contain two structural domains forming by three transmembrane helical repetitive structures.

By means of mutation experiment, the scientists carried out researches on the binding sites of chloramphenicol on the basis of its cell level and identified amino acid residue which played an important role in several substrates combination and protonation loci. On the basis of this crystal structure and related biochemical-biophysical analyses, they proposed a general mechanism of the multidrug resistance by this type of transporters.

This study on transporters will facilitate strategies on the drug-resistance problem and help people to better understand the nature of the endless war between human beings and bacteria.

Figure: Overall structure of MdfA-Cm (Image by ZHANG Kai and ZHAO Yongfang)