Lipid A Modification of Colistin-Resistant Klebsiella Pneumoniae Does Not Alter the Host Inflammatory Response

摘要: Background/Rationale Polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections occurs by chemical modification of the lipid A portion of lipopolysaccharide (LPS). Two pathways that mediate resistance include the insertional inactivation of the mgrB gene, altering an important regulatory system, or the transfer of mcr-1, a plasmid-mediated resistance gene. Whether these mutations disrupt the normal innate host immune response or carry a high fitness cost in the host is not well established. Methods Infection with K. pneumoniae ATCC 13883 harboring either the mcr-1 plasmid (pmcr-1) or the vector control (pBCSK) ATCC 13883 or mgrB isogenic mutants (ΔmgrB) was investigated. The baseline bacterial fitness characteristics were evaluated by kinetic growth curve, biofilm production, bacterial ROS production, and THP-1 uptake assay. THP-1 cells (human monocytes) were stimulated …