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Antimicrob Agents Chemother. 2015 Jul;59(7):4343-6. doi: 10.1128/AAC.04629-14. Epub 2015 Apr 27.

Emergence of polymyxin B resistance influences pathogenicity in Pseudomonas aeruginosa mutators.

Author information

1
Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA.
2
Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
3
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.
4
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.
5
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
6
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.

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 mutS P. aeruginosa resulted in attenuation of virulence.

PMID:
25918151
PMCID:
PMC4468730
DOI:
10.1128/AAC.04629-14
[Indexed for MEDLINE]
Free PMC Article

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