Fig. 3: Genetic determinants of heteroresistance in Enterobacter species.

Comparative genomics of colistin-resistant and -sensitive isolates revealed that arnBCADTEF is necessary for colistin heteroresistance. In Enterobacterales, arnBCADTEF expression is controlled by the TCS PhoPQ, while the activity of the PhoPQ pathway is inhibited by the small transmembrane protein MgrB. Deletion mutants were created in E. xiangfangensis L-1 isolate RBK-17-0394-1 (WT) and studied for the MIC_LB and HRF (number of cells recovered on LB agar plate containing 8 or 32 mg/L of colistin/number of cells inoculated). MIC_LB was measured by BMD while HRF was calculated by PAP test. Analysis of mutants showed the phoPQ/arnBCADTEF axis is absolutely required for the colistin heteroresistance, while MgrB acts as a negative regulator of arnBCADTEF resulting in colistin susceptibility. As reported previously by Kang et al.²² for E. cloacae, PmrAB did not contribute to colistin resistance in E. xiangfangensis. Source data are provided as a Source data file. The MIC data is provided in the Source data file.