Interplay of Klebsiella pneumoniae fabZ and lpxC Mutations Leads to LpxC Inhibitor-Dependent Growth Resulting from Loss of Membrane Homeostasis.

ABSTRACT: Tight coordination of inner and outer membrane biosynthesis is very important in Gram-negative bacteria. Biosynthesis of the lipid A moiety of lipopolysaccharide, which comprises the outer leaflet of the outer membrane has garnered interest for Gram-negative antibacterial discovery. In particular, several potent inhibitors of LpxC (the first committed step of the lipid A pathway) are described. Here we show that serial passaging of Klebsiella pneumoniae in increasing levels of an LpxC inhibitor yielded mutants that grew only in the presence of the inhibitor. These strains had mutations in fabZ and lpxC occurring together (encoding either FabZ_R121L/LpxC_V37G or FabZ_F51L/LpxC_V37G). K. pneumoniae mutants having only LpxC

SUBMITTER: Mostafavi M 

PROVIDER: S-EPMC6211225 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature