The effect of the polycation polyethyleneimine (PEI) on the permeabili
ty properties of the Gram-negative bacterial outer membrane was invest
igated using Escherichia coli, Pseudomonas aeruginosa and Salmonella t
yphimurium as target organisms. At concentrations of less than 20 mu g
ml(-1), PEI increased the bacterial uptake of 1-N-phenyl naphthylamin
e, which is a hydrophobic probe whose quantum yield is greatly increas
ed in a lipid environment, indicating increased hydrophobic permeation
of the outer membrane by PEI. The effect of PEI was comparable to tha
t brought about by the well-known permeabilizer EDTA. Permeabilization
by PEI was retarded but not completely inhibited by millimolar concen
trations of MgCl2. PEI also increased the susceptibility of the test s
pecies to the hydrophobic antibiotics clindamycin, erythromycin, fucid
in, novobiocin and rifampicin, without being directly bactericidal. PE
I sensitized the bacteria to the lytic action of the detergent SDS in
assays where the bacteria were pretreated with PEI. In assays where PE
I and SDS were simultaneously present, no sensitization was observed,
indicating that PEI and SDS were inactivating each other. In addition,
a sensitizing effect to the nonionic detergent Triton X-100 was obser
ved for P. aeruginosa. In conclusion, PEI was shown to be a potent per
meabilizer of the outer membrane of Gram-negative bacteria.