Penetrability of the Outer Membrane of Neisseria gonorrhoeae in Relation to Acquired Resistance to Penicillin and Other Antibiotics

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Abstract
Acquired antibiotic resistance in Neisseria gonorrhoeae is principally associated with three genetic markers, penA, mtr , and penB. penA is a specific marker for penicillin resistance, whereas mtr and penB are nonspecific in conferring resistance to penicillin and several other antibiotics as well. It has been suggested that the nonspecific markers may cause a general decrease in the penetrability of the gonococcal outer membrane. To investigate this, antibiotic penetration of the outer membrane was studied in two isogenic strains—FA19 (susceptible parent) and FA140 (containing penA, mtr , and penB )—and also in a clinical isolate with multiple resistance. The method involved brief treatment of exponential cells with ethylenediaminetetraacetic acid at 5°C to disrupt the outer membrane barrier. The 50% inhibitory concentrations of antibiotics for treated and normal cells were measured turbidimetrically, and from their ratios outer membrane penetration barriers were calculated. Small barriers were observed for actinomycin D and benzylpenicillin, and these were very similar in the susceptible and resistant strains. Also, in FA140 no significant barriers for rifampin, erythromycin, and tetracycline were detected. These results suggest that mechanism(s) other than reduced outer membrane penetrability underlie acquired resistance due to penA, mtr , and penB .