Sodium hexametaphosphate sensitizes Pseudomonas aeruginosa, several other species of Pseudomonas, and Escherichia coli to hydrophobic drugs

Abstract

Many gram-negative bacteria are known to be remarkably resistant to hydrophobic noxious agents by virtue of their outer membranes (OM). We investigated, by using four different assay methods, the ability of sodium hexametaphosphate (HMP) to disrupt this OM barrier. (i) In the growth inhibition assay, HMP was found to sensitize strains of Pseudomonas aeruginosa to all the hydrophobic probes tested (rifampin, fusidic acid, dactinomycin, sodium dodecyl sulfate, and Triton X-100). A concentration of 0.3% HMP decreased the MICs of the probes by a factor of approximately 10, and maximally even a 30-fold sensitization was found with 1% HMP. (ii) In the bactericidal assay, 0.3% HMP decreased the MBC of the hydrophobic probe rifampin by a factor of approximately 30. (iii) In the bacteriolytic assay, 0.1% HMP sensitized the target bacteria to lysis by sodium dodecyl sulfate and Triton X-100. (iv) In the fluorescent-probe binding assay, HMP drastically enhanced the binding of fluorescent N-phenyl naphthylamine to the membranes of the target cells. In addition to P. aeruginosa, P. fluorescens, P. putida, P. fragi, and Escherichia coli were susceptible to the OM permeability-increasing action of HMP, while P. cepacia was resistant.