Viruses as key reservoirs of antibiotic resistance genes in the environment.

Antibiotic resistance is a rapidly growing health care problem globally and causes many illnesses and deaths. Bacteria can acquire antibiotic resistance genes (ARGs) by horizontal transfer mediated by mobile genetic elements, where the role of phages in their dissemination in natural environments has not yet been clearly resolved. From metagenomic studies, we showed that the mean proportion of predicted ARGs found in prophages (0-0.0028%) was lower than those present in the free viruses (0.001-0.1%). Beta-lactamase, from viruses in the swine gut, represented 0.10 % of the predicted genes. Overall, in the environment, the ARG distribution associated with viruses was strongly linked to human activity, and the low dN/dS ratio observed advocated for a negative selection of the ARGs harbored by the viruses. Our network approach showed that viruses were linked to putative pathogens (Enterobacterales and vibrionaceae) and were considered key vehicles in ARG transfer, similar to plasmids. Therefore, these ARGs could then be disseminated at larger temporal and spatial scales than those included in the bacterial genomes, allowing for time-delayed genetic exchanges.