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Emergence of Polymyxin B Resistance Influences Pathogenicity in Pseudomonas aeruginosa Mutators
Authors:Zackery P. Bulman  Mark D. Sutton  Neang S. Ly  Jurgen B. Bulitta  Patricia N. Holden  Roger L. Nation  Jian Li  Brian T. Tsuji
Abstract:The interplay between polymyxin B pharmacodynamics and pathogenicity was examined in Pseudomonas aeruginosa PAO1 and isogenic DNA repair-deficient mutators (mutM and mutS strains). Against mutS mutators, polymyxin B initial killing was concentration dependent, with >99.9% bacterial reduction at 2 h followed by regrowth and resistance. The pre- versus postexposed strains were inoculated real time into Galleria mellonella waxworms, resulting in increased median survival times from 20 h to 23 h (P < 0.001). Emergence of resistance in mutSP. aeruginosa resulted in attenuation of virulence.
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