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.

Tuning of the Lethal Response to Multiple Stressors with a Single-Site Mutation during Clinical Infection by Staphylococcus aureus

“…For example, use of anti- agr agents or therapeutic vaccines ( 62 ) may be ill advised for applications in which the absence of agr reduces antimicrobial lethality. Identifying other adaptations that erode the lethal activities of antimicrobials could lead to novel strategies for selectively bolstering antimicrobial effectiveness ( 68 – 70 ).…”

Resveratrol: A Double-Edged Sword in Health Benefits

“…E. coli and Staphylococcus aureus culture supplemented with resveratrol and treated with antimicrobials reduced ROS concentrations to sublethal levels, that are mutagenic, while the absence of resveratrol allows ROS to high enough to kill mutagenized cells. Antimicrobial lethality suppression and mutant recovery promotion abilities evidenced by resveratrol suggests that this antioxidant may contribute to the emergence of several antimicrobials-resistant species, especially if new derivatives and/or resveratrol formulations markedly increase its bioavailability [ 107 ].…”

Resveratrol—Potential Antibacterial Agent against Foodborne Pathogens

“…It is a compound present in grape skins and wine, and is known to exhibit multi-spectrum therapeutic applications having been reported to exhibit anticancer, antiangiogenic, immunomodulatory, cardioprotective, and antioxidant activity. Although there is still very limited work on the antibacterial activity of resveratrol, it has been shown that resveratrol exhibits antibacterial activity against several Gram-positive and Gram-negative foodborne bacteria (Chan, 2002 ; Tegos et al, 2002 ; Paulo et al, 2010 ; Paolillo et al, 2011 ; Alvarez et al, 2012 , 2013 ; Kumar et al, 2012b ; Plumed-Ferrer et al, 2013 ; Augustine et al, 2014 ; Ferreira et al, 2014 ; Moran et al, 2014 ; Promgool et al, 2014 ; Subramanian et al, 2014 ; Duarte et al, 2015 ; Kim et al, 2015 ; Makwana et al, 2015 ; Ferreira and Domingues, 2016 ; Liu et al, 2016 ; Seukep et al, 2016 ; Silva et al, 2016 ; Surendran Nair et al, 2016 ; Klancnik et al, 2017 ; Lai et al, 2017 ; Lee and Lee, 2017 ; Oliveira et al, 2017 ). This review aims to provide an overview of the published data on the antibacterial activity of resveratrol against foodborne pathogens, its mechanisms of action as well as its possible applications in food packing and processing; in addition we also summarize the current data on its potential synergism with known antibacterials and future research and applications.…”