Accumulation of Trospectomycin by Strains ofSalmonella typhimurium, escherichia coliandHaemophilus influenzae

Trospectomycin, unlike aminoglycosidic aminocyclitols, is accumulated by a nonsaturable, energy-independent, diffusional process in Salmonella typhimurium, Escherichia coli and Haemophilus influenzae. A deep rough mutant of S typhimurium was more susceptible and accumulated the drug faster, and F porin deficient mutants of E coli were more resistant than parental strains. Trospectomycin likely uses both porin and nonporin pathways to cross the outer membrane. An E coli strain effectively accumulated the drug anaerobically, explaining its anaerobic activity. An H influenzae strain accumulated trospectomycin at concentrations below those for which detectable uptake could be observed with E coli or S typhimurium strains, consistent with greater activity in Haemophilus species.