title: Synergistic interactions of vancomycin with different antibiotics against Escherichia coli: trimethoprim and nitrofurantoin display strong synergies with vancomycin against wild-type E. coli.
abstract: Gram-negative bacteria are normally resistant to the antibiotic vancomycin (VAN), which cannot significantly penetrate the outer membrane. We used Escherichia coli mutants that are partially sensitive to VAN to study synergies between VAN and 10 other antibiotics representing six different functional categories. We detected strong synergies with VAN and nitrofurantoin (NTR) and with VAN and trimethoprim (TMP) and moderate synergies with other drugs, such as aminoglycosides. These synergies are powerful enough to show the activity of VAN against wild-type E. coli at concentrations of VAN as low as 6.25 μg/ml. This suggests that a very small percentage of exogenous VAN does enter E. coli but normally has insignificant effects on growth inhibition or cell killing. We used the results of pairwise interactions with VAN and the other 10 antibiotics tested to place VAN into a functional category of its own, as previously defined by Yeh et al. (P. Yeh, A. I. Tschumi, and R. Kishony, Nat Genet 28:489-494, 2006, http://dx.doi.org/10.1038/ng1755).
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Tina Manzhu
authors.initials: TM
authors.lastname: Kang
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Beppler
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Minh Quan
authors.initials: MQ
authors.lastname: Nguyen
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, USA pamelayeh@ucla.edu jhmiller@microbio.ucla.edu.
authors.forename: Pamela
authors.initials: P
authors.lastname: Yeh
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California, USA pamelayeh@ucla.edu jhmiller@microbio.ucla.edu.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D009154:Mutation; D009582:Nitrofurantoin / Q000494:pharmacology*; D019696:Peptidylprolyl Isomerase / Q000235:genetics; D014295:Trimethoprim / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D014640:Vancomycin; D009582:Nitrofurantoin; D014295:Trimethoprim; C490900:SurA protein, E coli; D019696:Peptidylprolyl Isomerase