Emergence of Polymyxin B Resistance Influences Pathogenicity in

The interplay between polymyxin B pharmacodynamics and pathogenicity was examined in Pseudomonas aeruginosa PAO1 and isogenic DNA repair-deficient mutators (mutM andmutS strains). AgainstmutSmutators, polymyxin B initial killing was con-centration 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 mellonellawaxworms, resulting in increased median survival times from 20 h to 23 h (P< 0.001). Emergence of resistance inmutS P. aeruginosa resulted in attenuation of virulence. Pseudomonas aeruginosa is a versatile opportunistic humanpathogen with an exceptional ability to adapt to antimicrobial therapy and has remarkable pathogenicity (1, 2). Virulence in P. aeruginosa is primarily under the control of quorum-sensing two-component systems, such as las and rhl, which allow for regulation of a wide array of virulence genes in a cell-density-dependent manner (3, 4). The immediate impact of antibiotic exposure on P. aeruginosa virulence factor production likely varies, depending on the pharmacological mechanism (5–7). Although cellular control of P. aeruginosa virulence is well characterized, the impact that antibiotic exposure and emergence of resistance have on bacteria