Antibiotic tolerance due to restriction of cAMP-Crp regulation by mannitol, a non-glucose-family PTS carbon source.

ABSTRACT: Enzyme-IIA (EIIA^Glc, Crr) of the phosphotransferase system (PTS) connects the uptake of glucose-family sugars to the cAMP-Crp regulatory cascade; phosphorylated EIIA^Glc enhances cAMP-Crp activity, which then contributes to the antibiotic-mediated accumulation of reactive oxygen species (ROS) and cell death. Defects in PTS cause antibiotic and disinfectant tolerance. We report that mannitol, a carbon source whose uptake does not use EIIA^Glc, reduces antibiotic-mediated killing of Escherichia coli without affecting antibiotic minimal inhibitory concentration. Thus, mannitol promotes antibiotic tolerance. The tolerance pathway was defined by the loss of ciprofloxacin lethality from the deletion of ptsI (first gene in PTS), mtlA (mannitol-s

SUBMITTER: Zhu W 

PROVIDER: S-EPMC11656735 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature