Environmental fate processes of antimicrobial peptides daptomycin, bacitracins, and polymyxins

Abstract

Antimicrobial peptides (AMPs) are increasingly important as a last resort against multi-drug resistant bacteria due to resistance formation towards conventional antibiotics. However, many AMPs were introduced to the market before environmental risk assessment was required, e.g., by the European Medicines Agency (EMA) since 1998. While AMPs have been administered as antibiotics and growth promotors in feedstock since the 1960s and were reconsidered for human medicine by the EMA in 2013, details about their mobility and persistence in the environment remain unknown. This study investigated the environmental fate of three commonly used AMPs: bacitracins, daptomycin, and polymyxins B and E (Colistin). We observed moderate sorption affinity of daptomycin to standard European soils (Kd = 20.6–48.6), while polymyxins adsorbed irreversibly. Bacitracin variants sorbed slightly to sandy soil (Kd = 5.8–8) and significantly to clayey soil (Kd = 169–250). We further investigated photochemical and microbial transformation processes relevant in surface waters. We demonstrated that phototransformation of all AMPs was enhanced in the presence of dissolved organic matter and fast bimolecular reaction rate constant with singlet oxygen contributed largely to indirect phototransformation (15–41%). Phototransformation product analysis for daptomycin was consistent with expected modifications of the tryptophan and kynurenine moieties. Moreover, riverine biofilm communities demonstrated biotransformation potential for all AMPs. Our findings of sorption behaviour, photo- and biotransformation suggest that these processes play a critical role in the fate of bacitracins, daptomycin, and polymyxins in environmental systems.