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The role of lipopolysaccharide (LPS) in determining the permeability of the outer membrane of Pseudomonas aeruginosa to carbenicillin and gentamicin was investigated. The susceptibility of P. aeruginosa isolates to smooth LPS-specific phages and to pyocin R1 gave indirect evidence of an altered LPS structure in strains resistant to carbenicillin, gentamicin, or both. Some secondary mutation, however, also appeared to be required for acquisition of the antibiotic-resistant phenotype. Phage- and pyocin-resistant variants demonstrating both wild-type and mutant responses to the drugs were subsequently isolated. Four-, eight-, and 16-fold increases in resistance to carbenicillin, supersusceptible responses to gentamicin, or both, were associated with a number of the LPS-altered mutants. The results supported the hypothesis that a primary mutation involving LPS, in combination with some undefined secondary mutation, determines the permeability of the outer membrane to carbenicillin and to gentamicin.

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