Ecology, more than antibiotics consumption, is the major predictor for the global distribution of aminoglycoside-modifying enzymes

Antibiotic consumption and its abuses have been historically and repeatedly pointed out as the major driver of antibiotic resistance emergence and propagation. However, several examples show that resistance may persist despite substantial reductions in antibiotic use, and that other factors are at stake. Here, we study the temporal, spatial, and ecological distribution patterns of aminoglycoside resistance, by screening more than 160,000 publicly available genomes for 27 clusters of genes encoding aminoglycoside-modifying enzymes (AME genes). We find that AME genes display a very ubiquitous pattern: about 25% of sequenced bacteria carry AME genes. These bacteria were sequenced from all the continents (except Antarctica) and terrestrial biomes, and belong to a wide number of phyla. By focusing on European countries between 1997 and 2018, we show that aminoglycoside consumption has little impact on the prevalence of AME-gene-carrying bacteria, whereas most variation in prevalence is observed among biomes. We further analyze the resemblance of resistome compositions across biomes: soil, wildlife, and human samples appear to be central to understand the exchanges of AME genes between different ecological contexts. Together, these results support the idea that interventional strategies based on reducing antibiotic use should be complemented by a stronger control of exchanges, especially between ecosystems.

Automated summary

Antibiotic consumption alone does not fully explain the persistence of antibiotic resistance, as shown by the widespread presence of aminoglycoside-modifying enzyme (AME) genes in bacteria from various ecological contexts. This study demonstrates that the prevalence of AME-carrying bacteria is influenced by ecological factors more than antibiotic use. Analysis of resistome compositions reveals the importance of exchanges between soil, wildlife, and human samples in the dissemination of AME genes. Intervention strategies should consider both reducing antibiotic use and controlling exchanges between ecosystems.