title: Synergy between Colistin and the Signal Peptidase Inhibitor MD3 Is Dependent on the Mechanism of Colistin Resistance in Acinetobacter baumannii.
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.
authors.affiliation: Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Coruña, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Guitián
authors.affiliation: Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Coruña, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Vázquez-Ucha
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Odingo
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
authors.affiliation: Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Coruña, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Poza
authors.affiliation: Antimicrobial Research Group, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Waite
authors.affiliation: Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Coruña, Spain.
authors.forename: German
authors.initials: G
authors.lastname: Bou
authors.affiliation: Antimicrobial Research Group, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Wareham
authors.affiliation: Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Coruña, Spain alejandro.beceiro.casas@sergas.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Beceiro
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D003091:Colistin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011480:Protease Inhibitors; D003091:Colistin