Antibiotic resistance is one of the biggest threats to global public health, food security and global development today. Due to the spread of antibiotic resistance, a growing number of infections such as pneumonia and tuberculosis are becoming more difficult to treat, leading to longer hospital stays, higher costs and increased mortality.
“Many public health agencies have recommended reducing antibiotic use in response to the challenges posed by resistance,” said co-author La Pradier, a former doctoral student at the University of Montpellier in France. Pradier conducted the study together with CNRS researcher Stephanie Bedhomme. “However, there are cases where developed countries have reduced antibiotic consumption and not stopped the spread of antibiotic resistance genes among bacterial populations, suggesting the role of other factors,” continues Pradier.
Antibiotic Resistance: New Insights
To explain this, Pradier and Bedhomme set out to describe the genetic, geographic and environmental distribution of resistance to a class of antibiotics called aminoglycosides, and from this information to quantify the relative contribution of different factors to the spread of antibiotic resistance. Aminoglycosides have limited clinical use in humans, but are often a last resort for the treatment of very persistent infections. They are also widely used in the treatment of farm animals, meaning that resistance to them poses a serious threat to global food security.
They used a computational approach to screen the genetic information of more than 160,000 bacterial genomes, looking for genes encoding aminoglycoside-modifying enzymes (AMEs), the most common mechanism of resistance to aminoglycosides. They found AME genes in about a quarter of the genomes examined and in samples from all continents (except Antarctica) and all biomes examined. The majority of AME-gene-carrying bacteria were found in clinical samples (55.3%), human samples (22.1%) and farm samples (12.3%).
Pradier and Bedhomme then focused on the prevalence of AME genes in Europe from 1997 to 2018, when the most detailed data were available. During this period, the use of aminoglycosides remained relatively stable, but was highly variable between countries. Comparing the prevalence of AME genes across countries using different aminoglycosides over time, the team found that aminoglycoside consumption was only a minor explanatory factor with several positive or directional effects on AME gene prevalence.
Instead, the database suggests that human exchange through trade and migration and exchanges between biomes explain much of the spread and maintenance of antibiotic resistance when modeled over time, space, and ecology. AME genes can be transported across continents via plant and animal products, international trade, and travelers, and then spread to local bacterial strains through a process called horizontal gene transfer—the movement of genetic information between organisms. The pool of AME genes sampled from plants, wildlife, and soil had the strongest overlap with other communities, suggesting that these biomes are major centers for AME gene spread through either horizontal resistance gene transfer or movement of resistant bacteria.
The findings suggest that the largest cause of AME gene spread is the movement of antibiotic-resistant bacteria between ecosystems and biomes. This spread is aided by mobile genetic elements, which increase the likelihood that a genome will carry multiple copies of the same AME gene. This increases the expression of transferred AME genes and allows bacteria to develop new antibiotic resistance functions through repetitive sequences.
These findings are preliminary because they are limited by the use of publicly available data rather than the application of a specific sampling method. In addition, genetic data from many different research projects have biased sampling against industrialized countries and biomes of clinical interest, leading to overrepresentation of some locations and biomes.
“Our study provides a broad overview of the spatial, temporal and ecological distribution of AME genes and establishes that the recent variation of AME bacteria in Europe is explained first by ecology, then by human exchange and finally by antibiotic consumption,” said Bedhomme. “Although the results of this study should not be generalized to antibiotic genes other than AMEs, the methods used can be readily applied to future studies of other antibiotic resistance gene families.”