Polymyxin resistance caused by large-scale genomic inversion due to IS26 intramolecular translocation in Klebsiella pneumoniae

Polymyxin B and polymyxin E(colistin)are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales,Acinetobacter baumannii,and Klebsiella pneumoniae.Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing.Polymyxin S2(S2)is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin.To predict the possible resistant mechanism of S2for wide clinical application,we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms.Mut-S,a resistant mutant of K.pneumoniae ATCC BAA-2146(Kpn2146)induced by S2,was analyzed by whole genome sequencing,transcriptomics,mass spectrometry and complementation experiment.Surprisingly,large-scale genomic inversion(LSGI)of approximately 1.1 Mbp in the chromosome caused by IS26mediated intramolecular transposition was found in Mut-S,which led to mgrB truncation,lipid A modification and hence S2resistance.The resistance can be complemented by plasmid carrying intact mgrB.The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146(Mut-B and Mut-E,respectively).This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K.pneumoniae.The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

RFPose-OT:RF-based 3D human pose estimation via optimal transport theory

This paper introduces a novel framework,i.e.,RFPose-OT,to enable three-dimensional(3D)human pose estimation from radio frequency(RF)signals.Different from existing methods that predict human poses from RF signals at the signal level directly,we consider the structure difference between the RF signals and the human poses,propose a transformation of the RF signals to the pose domain at the feature level based on the optimal transport(OT)theory,and generate human poses from the transformed features.To evaluate RFPose-OT,we build a radio system and a multi-view camera system to acquire the RF signal data and the ground-truth human poses.The experimental results in a basic indoor environment,an occlusion indoor environment,and an outdoor environment demonstrate that RFPose-OT can predict 3D human poses with higher precision than state-of-the-art methods.