Hormetic dose responses induced by antibiotics in bacteria: A phantom menace to be thoroughly evaluated to address the environmental risk and tackle the antibiotic resistance phenomenon

• Published in: The Science of the total environment Vol. 798; p. 149255
• Main Authors: Iavicoli, Ivo, Fontana, Luca, Agathokleous, Evgenios, Santocono, Carolina, Russo, Francesco, Vetrani, Ilaria, Fedele, Mauro, Calabrese, Edward J.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2021
• Subjects: Antimicrobial resistance; Hormesis; Mixture toxicology; Plasmid conjugative transfer; Subinhibitory concentrations; Hormesis; Subinhibitory concentrations; Antimicrobial resistance; Mixture toxicology; Plasmid conjugative transfer
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2021.149255

The environmental contamination of antibiotics caused by their over or inappropriate use is a major issue for environmental and human health since it can adversely impact the ecosystems and promote the antimicrobial resistance. Indeed, considering that in the environmental matrices these drugs are present at low levels, the possibility that bacteria exhibit a hormetic response to increase their resilience when exposed to antibiotic subinhibitory concentrations might represent a serious threat. Information reported in this review showed that exposure to different types of antibiotics, either administered individually or in mixtures, is capable of exerting hormetic effects on bacteria at environmentally relevant concentrations. These responses have been reported regardless of the type of bacterium or antibiotic, thus suggesting that hormesis would be a generalized adaptive mechanism implemented by bacteria to strengthen their resistance to antibiotics. Hormetic effects included growth, bioluminescence and motility of bacteria, their ability to produce biofilm, but also the frequency of mutation and plasmid conjugative transfer. The evaluation of quantitative features of antibiotic-induced hormesis showed that these responses have both maximum stimulation and dose width characteristics similar to those already reported in the literature for other stressors. Notably, mixtures comprising individual antibiotic inducing stimulatory responses might have distinct combined effects based on antagonistic, synergistic or additive interactions between components. Regarding the molecular mechanisms of action underlying the aforementioned effects, we put forward the hypothesis that the adoption of adaptive/defensive responses would be driven by the ability of antibiotic low doses to modulate the transcriptional activity of bacteria. Overall, our findings suggest that hormesis plays a pivotal role in affecting the bacterial behavior in order to acquire a survival advantage. Therefore, a proactive and effective risk assessment should necessarily take due account of the hormesis concept to adequately evaluate the risks to ecosystems and human health posed by antibiotic environmental contamination. [Display omitted] •Different types of antibiotics induce hormesis in several bacteria strains.•Hormesis occurs at environmentally relevant concentrations of antibiotics.•Hormetic effects are a defensive strategy aimed to increase bacterial resilience.•Hormetic responses have important implications for environmental and human health.