bRecent studies of natural environments have revealed vast genetic reservoirs of antibiotic resistance (AR) genes. Soil bacteria and human pathogens share AR genes, and AR genes have been discovered in a variety of habitats. However, there is little knowledge about the presence and diversity of AR genes in marine environments and which organisms host AR genes. To address this, we identified the diversity of genes conferring resistance to ampicillin, tetracycline, nitrofurantoin, and sulfadimethoxine in diverse marine environments using functional metagenomics (the cloning and screening of random DNA fragments). Marine environments were host to a diversity of AR-conferring genes. Antibiotic-resistant clones were found at all sites, with 28% of the genes identified as known AR genes (encoding beta-lactamases, bicyclomycin resistance pumps, etc.). However, the majority of AR genes were not previously classified as such but had products similar to proteins such as transport pumps, oxidoreductases, and hydrolases. Furthermore, 44% of the genes conferring antibiotic resistance were found in abundant marine taxa (e.g., Pelagibacter, Prochlorococcus, and Vibrio). Therefore, we uncovered a previously unknown diversity of genes that conferred an AR phenotype among marine environments, which makes the ocean a global reservoir of both clinically relevant and potentially novel AR genes.
The spread of antibiotic resistance (AR) is critically important to human health. Past research has focused on resistance in clinical environments (e.g., hospitals), but the rise of communityacquired infections of resistant bacteria has fueled interest in AR genes in natural environments (1-3). Natural environments can be important, as they can act as reservoirs of AR genes (1, 2). Such environments include soils (4, 5), glaciers (6), and animals (7-9). Additionally, the frequency of AR in human hosts is also higher than previously thought (10, 11), and the AR genes found in soil bacteria have also been found in clinical pathogens (2). One set of environments that has received little attention is marine environments. Oceans are dilute systems, and hence, there may be little selection for antibiotic production, as compounds can rapidly diffuse away from the producer (12). However, there are three possible mechanisms that can lead to the occurrence of AR in marine environments. One is through coastal runoff of AR bacteria from terrestrial sources. In this case, we expect to find AR genes in bacterial taxa nonnative to marine environments. The second mechanism is through selection for AR due to anthropogenic antibiotic runoff, which challenges native bacteria to become resistant. The third is selection for resistance in response to antibiotic production in marine environments. Antagonistic microbial interactions can occur on marine snow (13) or in small parcels of seawater (14, 15). These interactions may include the production of antibiotics and subsequent selection for resistance.Despite the large expanse of the oceans, we currently have littl...