title: Pairwise antibiotic interactions in Escherichia coli: triclosan, rifampicin and aztreonam with nine other classes of antibiotics.
abstract: Previous investigations have shown that analyzing pairwise interactions between 22 antibiotics in Escherichia coli enable the grouping of drugs into nine functional classes. Our aim is to significantly expand this drug network by adding three clinically relevant antibiotics, two of which have distinct mechanisms of action not previously represented. Here, we examine triclosan, rifampicin and aztreonam, by testing them pairwise against themselves and one antibiotic from each of the nine classes. Network analysis shows that triclosan, rifampicin and aztreonam each form distinct functional groups of their own. This is particularly surprising for aztreonam, which is a cell wall synthesis inhibitor but did not cluster with other cell wall synthesis inhibitors. Furthermore, of the 30 pairs tested, we found several previously unreported synergies that could potentially be used in multidrug therapies. The distinct functional groups suggest that there may be properties of these drugs that are different from other drugs even with similar mechanism of action, and that, when considering drug combinations, aztreonam in particular is not simply interchangeable with other cell wall synthesis inhibitors.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular, Biology Institute, and the David Geffen School of Medicine, University of California, CA, 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, CA, 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, CA, USA.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, the Molecular, Biology Institute, and the David Geffen School of Medicine, University of California, CA, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miller
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, CA, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Yeh
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D016000:Cluster Analysis; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D012293:Rifampin / Q000494:pharmacology*; D014260:Triclosan / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014260:Triclosan; D001398:Aztreonam; D012293:Rifampin