title: Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.
abstract: Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical) are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. The possibility has been raised that consumption of antioxidants in food may interfere with the lethal action of antimicrobials. Whether nutritional supplements containing antioxidant activity are also likely to interfere with antimicrobial lethality is unknown. To examine this possibility, resveratrol, a popular antioxidant dietary supplement, was added to cultures of Escherichia coli and Staphylococcus aureus that were then treated with antimicrobial and assayed for bacterial survival and the recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present during human consumption, caused a 2- to 3-fold reduction in killing during a 2-hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders of magnitude. Resveratrol also reduced the increase in reactive oxygen species (ROS) characteristic of treatment with quinolone (oxolinic acid). These data support the general idea that the lethal activity of some antimicrobials involves ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6-fold) the recovery of rifampicin-resistant mutants arising from the action of ciprofloxacin, kanamycin, or daptomycin. This result is consistent with resveratrol reducing ROS to sublethal levels that are still mutagenic, while the absence of resveratrol allows ROS levels to high enough to kill mutagenized cells. Suppression of antimicrobial lethality and promotion of mutant recovery by resveratrol suggests that the antioxidant may contribute to the emergence of resistance to several antimicrobials, especially if new derivatives and/or formulations of resveratrol markedly increase bioavailability.
authors.affiliation: Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, 194 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, 194 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Jinan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, 194 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, 194 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Xinguang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, 194 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Guojing
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, 194 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Public Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, 225 Warren St, Newark, NJ 07103, United States of America.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Public Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, 225 Warren St, Newark, NJ 07103, United States of America.
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
authors.affiliation: Public Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, 225 Warren St, Newark, NJ 07103, United States of America.|State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, South Xiang-An Road, Xiang-An District, Xiamen, Fujian Province, 361102, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol