Open AccessImpact of Two-Component Regulatory Systems PhoP-PhoQ and PmrA-PmrB on Colistin Pharmacodynamics in Pseudomonas aeruginosa
Author(s) -
Neang S. Ly,
Jenny C. Yang,
Jürgen B. Bulitta,
Brian T. Tsuji
Publication year - 2012
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.06380-11
Subject(s) - colistin , pseudomonas aeruginosa , mutant , microbiology and biotechnology , wild type , pharmacodynamics , in vitro , two component regulatory system , pseudomonas , biology , bacteria , chemistry , antibiotics , pharmacology , biochemistry , gene , pharmacokinetics , genetics
Thein vitro pharmacodynamics of colistin againstPseudomonas aeruginosa PAO1 wild-type and isogenic knockout strains ofphoP andpmrA were evaluated. Colistin killing at subinhibitory concentrations was greater against thephoP andpmrA mutants than the wild type within the first 8 h: the concentration that results in 50% of maximal effect (EC50 ) of thepmrA mutant (0.413 mg/liter) was less than that of the wild type (0.718 mg/liter) (P < 0.05). Anin vitro pharmacodynamic model simulating human colistin regimens displayed initial killing followed by regrowth in thephoP mutant and gradual regrowth in thepmrA mutant and wild type.