Impacts of wastewater treatment and the exposome on antibiotic resistance gene dynamics: Insights from Guadeloupe, a French Caribbean Island

Wastewater treatment plants (WWTPs) are global hotspots for disseminating antibiotic resistance genes (ARGs). Chemical compounds commonly found in wastewater, including antibiotics, biocides, non-steroidal anti-inflammatory drugs (NSAIDs), and heavy metals, along with climate variables and physicochemical factors can select for antibiotic-resistant bacteria even at low concentrations, promoting ARG proliferation. Since WWTPs can vary in their removal efficiency and influent compositions, we assessed their impact on ARGs and pollutant concentrations in Guadeloupe, French Caribbean. Using 96 samples collected across four campaigns (September 2021-January 2023) from three urban wastewater continuums (hospital-based, urban non-touristic, urban touristic), we profiled resistome and exposome in influent and effluent and applied machine learning (random forest, lasso) to identify variables most affected by treatment and factors associated with ARG patterns. Overall, ARG reduction was lower than anticipated. Among 16 clinically relevant genes targeted, aph(3’)-III, bla OXA , bla SHV , bla TEM , ermB, intI1, qnrS, and tetM decreased by 59.8% to 89.9% across WWTPs, while mcr-1 increased 9.52-fold in hospital effluent. Of nine antibiotics, most remained unchanged, and eight biocides were not effectively removed. Heavy-metal reductions occurred only in the non-touristic continuum (Cd -32.5%, Cu -21.1%, and Hg -36.2%). We found continuum-specific associations between ARGs and co-selective stressors including biocides, erythromycin, selected heavy metals (As, Cd, Cu, Cr, Hg), and water temperature. Upstream source was identified as a primary driver of effluent profiles. These results align with the EU’s revised Urban Wastewater Treatment Directive and reveal how co-occurring pollutants, and environmental factors shape ARG distributions in unique settings and regions with limited wastewater treatment management.