Livestock waste: A hidden source of extracellular clinically relevant high-risk antibiotic resistance genes in the environment

With the rise of antimicrobial resistance (AMR) to last-resort antibiotics endangering the ability to treat multidrug-resistant bacterial infections, identifying every source of resistance is essential. One such source is livestock waste. Since livestock are heavily treated with antibiotics, they provide an ideal environment for the enrichment of antibiotic resistance genes (ARGs). Livestock wastes are considered one of the primary reservoirs of ARGs and antibiotic-resistant bacteria (ARB) in the environment. Research into livestock waste antibiotic resistance has generally focused on intracellular ARGs (iARGs), which are located inside cells. ARGs can, however, also be found in extracellular DNA (eDNA), the outer cell DNA. The extent to which eDNA encodes extracellular ARGs (eARGs) and extracellular mobile genetic elements (eMGEs) in livestock wastes and mobilizes them in the environment remains unclear. Nevertheless, recent research has revealed that eDNA from livestock wastes can also play a vital role in disseminating antibiotic resistance in the environment. Therefore, addressing the role of eDNA from livestock waste in ARG dissemination is crucial for developing comprehensive strategies to combat antibiotic resistance. Taken together, this review provides comprehensive information on eDNA antibiotic resistance from the perspective of livestock wastes as sources of eARGs and the efficacy of different existing treatment processes that affect ARG abundances (both iARGs and eARGs), microbial communities, and the removal of eARGs. In addition, the review proposes future research directions to curb antibiotic resistance by understanding the fate of eARGs in livestock waste management. • In the environment, livestock waste constitutes a major source of eARGs • Manure's total suspended solids and organic content could influence the persistence of eNDA • In livestock wastes, high risk ARGs pose a serious threat to human health • Temperature and pH are the major driving factors in the flow of eARGs via HGT from manure to the environment.