Synergy between Colistin and the Signal Peptidase Inhibitor MD3 Is Dependent on the Mechanism of Colistin Resistance in Acinetobacter baumannii.

Authors :: Martínez-Guitián M
Vázquez-Ucha JC
Odingo J
Parish T
Poza M
Waite RD
Bou G
Wareham DW
Beceiro A
Source :: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2016 Jun 20; Vol. 60 (7), pp. 4375-9. Date of Electronic Publication: 2016 Jun 20 (Print Publication: 2016).
Publication Year :: 2016
Abstract: Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FICindex] = 0.13 to 0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of lipid A (FICindex = 0.14 to 0.25) but not against colistin-resistant Δlpx strains with loss of lipopolysaccharide (FICindex = 0.75 to 1). A colistin/MD3 combination would need to be targeted to strains with specific colistin resistance mechanisms.<br /> (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Subjects :: Acinetobacter baumannii metabolism
Bacterial Proteins genetics
Drug Resistance, Multiple, Bacterial genetics
Drug Synergism
Microbial Sensitivity Tests
Acinetobacter baumannii drug effects
Anti-Bacterial Agents pharmacology
Colistin pharmacology
Protease Inhibitors pharmacology

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