Global ocean resistome revealed: exploring Antibiotic Resistance Genes (ARGs) abundance and distribution on TARA oceans samples through machine learning tools

Abstract

The rise of antibiotic resistance (AR) in clinical settings is one of the biggest modern global public health concerns, therefore, the understanding of its mechanisms, evolution and global distribution is a priority due to its impact on the treatment course and patient survivability. Besides all efforts in the elucidation of AR mechanisms in clinical strains, little is known about its prevalence and evolution in environmental uncultivable microorganisms. In this study, 293 metagenomic and 10 metatranscriptomic samples from the TARA oceans project were used to detect and quantify environmental Antibiotic Resistance Genes (ARGs) using modern machine learning tools. After extensive manual curation, we show their global distribution, abundance, taxonomy and phylogeny, their potential to be horizontally transferred by plasmids or viruses and their correlation with environmental and geographical parameters. After manual curation, we identified a total of 99,205 environmental ORFs as potential ARGs. These ORFs belong to 560 ARG families that confer resistance to 26 antibiotic classes. A total of 149 ORFs were classified as viral sequences. In addition, 24,567 ORFs were found in contigs classified as plasmidial sequences, suggesting the importance of mobile genetic elements in the dynamics of ARGs transmission. From the 13,163 identified ARGs passing all the criteria for quantification analysis, 4,224 were expressed in at least one of the 10 metatranscriptomic samples (FPKM >5). Moreover, 4,804 contigs with more than 2 ARGs were found, including 2 plasmids with 5 different ARGs, highlighting the potential presence of multi-resistant microorganisms in natural environment and/or non-impacted by human presence oceans, together with the possibility of Horizontal Gene Transfer (HGT) between clinical and natural environments. The abundance of ARGs in 293 samples showed different patterns of distribution, with some classes being significatively more abundant in Coastal Biomes. Finally, we identified ARGs conferring resistance to some of the most relevant clinical antibiotics, revealing the presence of 15 ARGs from the recently discovered MCR-1 family with high abundance on Polar Biomes. A total of 5 MCR-1 ORFs are present in the genus Psychrobacter, an opportunistic bacteria that can cause fatal infections in humans.Our results are available on Zenodo in MySQL database dump format and all the code used for the analyses, including jupyter notebooks can be accessed on github (https://github.com/rcuadrat/ocean_resistome).Recently the number of metagenomic projects stored in public databases have been growing, but the lack of related metadata makes it difficult to conduct highthroughput gene screenings and correlations with environmental factors. Fortunately,