Rethinking tetracycline in the Anthropocene: From miracle drugs to emerging environmental contaminants

Tetracyclines (TCs) have been deployed for over seven decades in clinical and veterinary medicine due to their ability to inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit. Their intensive use, particularly in confined animal feeding operations and aquaculture, has resulted in persistent environmental inputs, as 40-90 % of administered TC is excreted unchanged or as bioactive metabolites. These compounds exhibit strong chelation with divalent cations and high affinity for soil organic matter, facilitating their long-term retention in soils, sediments, and manure-amended agricultural systems. Traditional remediation technologies-advanced oxidation, photocatalysis, membrane separation, and activated carbon adsorption achieve variable TC removal but are constrained by high energy consumption, catalyst deactivation, or secondary pollutant formation. Consequently, research has shifted toward mechanistically informed biocatalytic and hybrid bioremediation frameworks. Bacterial taxa such as Arthrobacter, Klebsiella spp., and Bacillus spp. have demonstrated TC degradation through enzymatic pathways involving oxidative deamination, CC ring cleavage, lactone hydrolysis, and transformation into less bioactive intermediates (e.g., anhydrotetracycline, epitetracycline). Algae and higher plants contribute via biosorption, intracellular sequestration, and conjugation to secondary metabolites. Recent advances integrate biochar-supported microbial biofilms, nanotechnology, metal-organic framework (MOF), that exploit electron transfer pathways to accelerate TC transformation. These hybrid technologies couple physicochemical and biological mechanisms to enhance removal kinetics, reduce toxic by-product generation, and strengthen the resilience of treatment systems. Collectively, such mechanistically grounded approaches offer promising strategies for mitigating TC contamination in heterogeneous natural and engineered environments.