The ability of an antimicrobial, cationic polyethylenimine (PEI+) to induce the three known extracytoplasmic stress responses of Escherichia coli was quantified. Exposure of E. coli to PEI+ in solution revealed specific, concentration-dependent induction of the Cpx extracytoplasmic cellular stress response, ~2.0-2.5 fold at 320 μg/mL after 1.5 hours without significant induction of the σE or Bae stress responses. In comparison, exposure of E. coli to a non-antimicrobial polymer, polyethylene oxide (PEO), resulted in no induction of the three stress responses. The antimicrobial small molecule vanillin, a known membrane pore-forming compound, was observed to cause specific, concentration-dependent induction of the σE stress response, ~6-fold at 640 μg/mL after 1.5 hours, without significant induction of the Cpx or Bae stress responses. The different stress response induction profiles of PEI+ and vanillin suggest that although both are antimicrobial compounds, they interact with the bacterial membrane and extracytoplasmic area by unique mechanisms. EPR studies of liposomes containing spin-labeled lipids exposed to PEI+, vanillin, and PEO reveal that PEI+ and PEO increased membrane stability whereas vanillin was found to have no effect.
The mechanisms of antimicrobial activity of a cationic polyethylenimine (PEI+) and a small molecule pore‐forming compound, vanillin, are thought to involve disruption of bacterial cell membranes. These proposed mechanisms were studied by measuring the induction of the three known extracytoplasmic stress responses (Cpx, σE and Bae) of the Gram‐negative bacterium Escherichia coli. PEI+ specifically induced the Cpx stress response approximately 2‐fold in a dose‐dependent manner at concentrations ranging from 80–320 μg/mL. Vanillin induced the σE stress response 4–12‐fold at concentrations ranging from 320–960 μg/mL. The implications of the observed differences in the induction of extracytoplasmic stress responses between PEI+ and vanillin on the antimicrobial mechanisms of these compounds will be discussed.
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