Emergence of polymyxin B resistance influences pathogenicity in Pseudomonas aeruginosa mutators

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 mutS P. aeruginosa resulted in attenuation of virulence.