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.
Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA.
Zackery P
ZP
Bulman
Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Mark D
MD
Sutton
Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Neang S
http://orcid.org/0000-0002-5571-0347
NS
Ly
Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
Jurgen B
JB
Bulitta
Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Patricia N
PN
Holden
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
Roger L
RL
Nation
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
Jian
J
Li
Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA btsuji@buffalo.edu.
Brian T
BT
Tsuji
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000382:microbiology; D004260:DNA Repair / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008826:Microbial Sensitivity Tests; D009036:Moths; D009154:Mutation / Q000235:genetics; D011112:Polymyxin B / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D013534:Survival; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D011112:Polymyxin B