title: Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents.
abstract: Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Liu
authors.forename: Amie
authors.initials: A
authors.lastname: Fong
authors.forename: Elinne
authors.initials: E
authors.lastname: Becket
authors.forename: Jessica
authors.initials: J
authors.lastname: Yuan
authors.forename: Cindy
authors.initials: C
authors.lastname: Tamae
authors.forename: Leah
authors.initials: L
authors.lastname: Medrano
authors.forename: Maria
authors.initials: M
authors.lastname: Maiz
authors.forename: Christine
authors.initials: C
authors.lastname: Wahba
authors.forename: Catherine
authors.initials: C
authors.lastname: Lee
authors.forename: Kim
authors.initials: K
authors.lastname: Lee
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Tran
authors.forename: Hanjing
authors.initials: H
authors.lastname: Yang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Anya
authors.initials: A
authors.lastname: Salih
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003116:Color; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents