New function of Gram-negative RND efflux pump first discovered

Recently, the research group of Liu Mafeng, a professor at the College of Veterinary Medicine of Sichuan Agricultural University, published a research paper online in the well-known journal Applied and Environmental Microbiology in microbiology. This study was the first to find that the Gram-negative RND (Resistance-nodulation-cell division) family efflux pump has the function of extruding manganese ions.

RND family efflux pumps play an important role in the multidrug resistance of gram-negative bacteria and are the main research objects for curbing drug resistance. In addition, RND efflux pumps are recognized as one of the most effective host defense systems for actively expelling harmful substances outside the cell. However, the species of native substrates for RND efflux have not been fully identified.

Liu Mafeng’s team, represented by Rickerella pestis, constructed 12 deletion strains encoding efflux pump genes in 5 classes (MFS, RND, PACE, SMR, MATE), and detected their sensitivity to manganese ions. The results showed that two genes (B739_RS08835,B739_RS04280) encoding RND efflux pumps were more sensitive to manganese ions after deletion, and the accumulation of manganese ions in the cell increased. The accumulation of manganese ions in the cell leads to obstruction of division and dysregulation of iron homeostasis. Among them, B739_RS04280 are activated by DtxR family proteins, but B739_RS08835 are not regulated by DtxR family proteins. A more novel discovery is that the DtxR family protein encoded by the bacterium participates in the regulation of six metal homeostasis, namely manganese, zinc, copper, iron, cobalt and nickel, and is the regulatory protein with the most reported regulation of metal ions. Given the low homology of this DtxR family of proteins with other identified bacterial DtxR proteins, the authors named it MetR (metals efflux transporter regulator).

This study expands the scope of understanding of the natural substrate efflux of Gram-negative RND efflux pumps, as well as the diversity of mechanisms of DtxR family regulating metal homeostasis, which is of great significance for further understanding of the mechanism of bacterial metal homeostasis, and has a reference role in the future use of new metal materials to prevent and control bacterial infections.


Excessive manganese ion accumulation leads to obstruction of the division of Liemerella pestis in duck pestis Photo courtesy of Sichuan Agricultural University

Liu Mafeng and his research team mainly focus on the steady-state study of metal metabolism of Rickerella pestis, and have been systematically studied in the early stage of iron ion metabolism (transport, efflux, chelation and regulation) of this bacterium. This study further demonstrates the interaction between different metal metabolisms of bacteria, and opens up new research directions for further elucidating the mechanism of metal homeostasis in Liemerella pestis.

The first author of the paper is Guo Fang, a 2020 master’s student of Sichuan Agricultural University, and the corresponding authors are professors Cheng Anchun and Liu Mafeng. The research was supported by grants from the National Natural Science Foundation of China and the Sichuan Provincial Department of Science and Technology. (Source: Zhang Qingdan, China Science News)

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