Research Highlights
CryoEM Reveals Mechanism Behind Polymyxin-Resistant Infections

In the escalating fight against drug-resistant Gram-negative bacteria, polymyxins are a last resort. Alarming is the rise of polymyxin-resistant infections, a major public health threat. AS scientists Yuan-Chao Lou (BioTReC), Chinpan Chen (IBMS), and Kuen-Phon Wu (IBC) have delved into this crisis. Employing advanced cryo-electron microscopy, they've exposed the dynamic bacterial PmrA-dependent transcription activation complex (TAC), housing a PmrA dimer, RNA polymerase σ70-holoenzyme (RNAPH), and promoter DNA. Intriguingly, RNAPH's electrostatic interaction with PmrA's DNA binding domain nudges the domain three base pairs upstream. In vivo trials confirmed DNA-recognition mutations curbing transcription, while altered RNAPH interaction heightened it. This research illuminates the intricate interplay of DNA distortion and promoter escape, advancing our grasp of PmrA-mediated transcription. Published in Nucleic Acids Research (September 2023), this breakthrough could shape strategies to tackle polymyxin-resistant bacteria.

This work is mainly contributed by Y-C Lou and H-Y Huang. Other authors include group members of Chen and Wu.

Article title: Structural basis of transcriptional activation by the OmpR/PhoB-family response regulator PmrA

Article link: https://doi.org/10.1093/nar/gkad724

Authors: Lou YC*, Huang HY, Yeh HH, Chiang WH, Chen C*, Wu KP*