In a recent study, published in the journal eLIFE, researchers have screened over 160,000 bacterial genomes to identify the presence of genes that confer resistance to a certain class of antibiotic. The work challenges the idea that overuse of antibiotics is the main driver of antimicrobial resistance (AMR) and highlights the need for stricter control of bacterial transmission.
Antibiotic resistance is a global health challenge
AMR is one of the most significant public health challenges globally. In 2019, almost 5 million deaths were thought to be associated with AMR, and this number is forecasted to rise to over 10 million by 2050.
Resistance can arise in a variety of ways, but AMR is mostly attributed to the overuse and misuse of antibiotics. Over time, this can lead to the evolution and natural selection of resistance genes in bacteria. There is a common misconception that over-consumption of antibiotics for medical purposes is the main driver of AMR – in reality, the use of antibiotics in an agricultural context is thought to be a far more significant contributor.
Antibiotic resistance genes are often contained within mobile genetic elements that can be spread via horizontal gene transfer – a process through which genetic information is passed from one organism to any other organism that is not their offspring. This means that even bacteria that have not been exposed to the relevant antibiotic can acquire resistance genes. Despite substantial work to prevent the evolution of antimicrobial resistance, the question remains as to how to prevent previously acquired genes from continuing to spread.
To gain an understanding of the patterns of horizontal gene transfer and the impacts of environmental and ecological factors on the spread of AMR, co-authors Léa Pradier and Stéphanie Bedhomme set out to analyse the presence of genes conferring resistance to aminoglycosides in different bacterial strains from around the world.
A global phenomenon
The duo analysed over 160,000 publicly available bacterial genomes, looking for evidence of the presence of 27 gene clusters known to contain aminoglycoside-modifying enzymes (AMEs). The dataset included genomes from every continent and terrestrial biome, allowing for a robust analysis of the environmental and ecological forces potentially driving AMR.
Ultimately, over a quarter of the genomes contained AMEs. These were primarily found in proteobacteria, firmicutes and actinobacteriota. The presence of AMEs was ubiquitous, with aminoglycoside resistant bacterial species found in every continent and biome. However, the prevalence of AMEs fluctuated between certain countries; there were particularly high levels of resistance in Indonesia and Mexico, compared to much lower levels in Japan.
Figure 1. Image showing the prevalence of resistance in different regions. ‘Resistant’ samples are those whose genome contained at least one AME. Adapted from Pradier and Bedhomme, 2023.
A further analysis of a subset of samples from European sources revealed that the prevalence of AMEs did not correlate with aminoglycoside usage. This supported the pair’s hypothesis that there is a major driver of resistance that is independent of antibiotic consumption. This was further supported by the revelation that AMEs were present in samples dating as far back as 1905 – 40 years prior to the introduction of aminoglycosides in healthcare or agriculture. The study stated that aminoglycoside usage could, in fact, be described as a “minor” contributor to overall resistance.
How can we fight AMR?
There are a number of explanations as to why antibiotic resistance is prevalent even in populations where usage is low. These genes could have evolved in response to a natural substance or could be “hitchhiking” on a mobile genetic element that confers resistance to other threats to bacterial survival, such as heavy metals. The varying prevalence of resistance within different biomes also suggests that there are ecological factors at play in the spread of these genes, and the presence of AMEs in biomes where there is low exposure to aminoglycosides implies transmission between ecosystems.
However, the authors also believe that human interactions are likely to be a significant, yet overlooked, driver of resistance. For example, bacteria can be spread from one population to another via exchanges between two humans and through travel, migration and food imports. These bacteria can then pass on resistance genes to organisms within the new population, even if those microbes had never previously been exposed to the drug.
These findings support the idea that the control of antibiotic usage should be complemented by initiatives to prevent the spread of bacteria across populations and ecosystems. Whilst this study only looks at one class of antibiotic, Bedhomme stated that “the methods used could easily be applied to further studies on other antibiotic resistance gene families.”