Polymyxin is the "last resort" of antibiotics. The self-induced resistance to polymyxin in Gram-negative bacteria could be mediated by lipopolysaccharide (LPS) modification, which is regulated by the two-component system, PhoP/PhoQ. is a common foodborne pathogen. However, PhoP/PhoQ has not been thoroughly studied in . In this study, the functions of PhoP/PhoQ in intrinsic resistance were investigated. The resistance of was found to decrease with the deletion of PhoP/PhoQ. Further, PhoP/PhoQ was found to play an important role in maintaining membrane permeability, intercellular metabolism, and reducing membrane depolarization. Based on subsequent studies, the binding ability of polymyxin to was decreased by the modification of LPS with structures, such as L-Ara4N and palmitate. Analysis of the gene transcription levels revealed that the LPS modification genes, and operon, were downregulated with the deletion of PhoP/PhoQ in during exposure to polymyxin. In addition, , , and were downregulated in the mutants compared with the wild-type strain. Such findings demonstrate that PhoP/PhoQ contributes to the intrinsic resistance of toward polymyxins. LPS modification with L-Ara4N or palmitate is mainly responsible for the resistance of to polymyxins. The transcription of genes related to LPS modification and PmrA/PmrB can be both affected by PhoP/PhoQ in . This study adds to current knowledge regarding the role of PhoP/PhoQ in intrinsic resistance of to polymyxin.
