Antimicrobial Resistance Spread in the Anthropocene
Nicoletta Makowska-Zawierucha
Adam Mickiewicz University, Poland
Winning article: Arctic plasmidome analysis reveals distinct relationships among associated antimicrobial resistance genes and virulence genes along anthropogenic gradients (Global Change Biology, 2024)
“By identifying the role of mobile genetic elements in environmental resistance, this work supports biotech innovations for rapid detection and continuous monitoring of antimicrobial resistance transmission.”
The rapid spread of antimicrobial resistance (AMR) is a major global health threat, identified by WHO as one of the greatest challenges of the 21st century. The overuse and misuse of antibiotics in the health system, livestock breeding, and agriculture are key drivers of the emergence and spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the environment. Tackling the global antibiotic resistance crisis demands a multidisciplinary approach, yet its environmental drivers—spanning even the most remote ecosystems—must be globally monitored to curb its evolution and spread.
Although much of AMR research has traditionally focused on human health and agriculture, it has become increasingly clear that the environment plays a significant role in the spread of ARB and ARGs. However, the environmental factors contributing to AMR spread, particularly in remote and fragile ecosystems like the polar regions, have not been well understood. The Arctic, with its unique physical features, niches, ecosystem simplicity, and growing anthropogenic impacts, provides a crucial opportunity to study how climate change and pollution influence the spread of AMR.
Our research focuses on the spread of AMR and virulence in Arctic environments, with particular emphasis on the role of plasmids. In this context, we explored antibiotic and metal resistance, as well as virulence spread across environmental gradients. We compared various aspects of the plasmidome (a collection of plasmids) from pristine settings through to heavily anthropogenically impacted environments in Spitsbergen, the largest island of the Arctic Svalbard archipelago.
Plasmids are mobile genetic elements that facilitate horizontal gene transfer between bacteria, and they play a key role in the spread of AMR. Integrons, which are often located on plasmids, also play an important role in the spread of multidrug resistance. Integrons are DNA fragments equipped with gene cassettes that are capable of capturing a multitude of ARGs and other genes conferring resistance to antimicrobials, including disinfectants and heavy metals. While metagenomic sequencing has provided significant insight into environmental resistomes (the collection of genes that contribute to antibiotic resistance), these methods often overlook the plasmidome, the mobile part of the resistome.
Our findings reveal that plasmid-encoded antibiotic resistance is widespread in the Arctic environments, where the selection pressure for antibiotics is thought to be low. This resistance may be derived from both anthropogenic sources and the release of ancient gene variants from the melting cryosphere. Various sources of resistance have significant implications for ecosystem functioning and risk for public health in the future. Moreover, the presence of metal resistance genes (MRGs) on plasmids, combined with the prevalence of metals in the environment, could further facilitate the spread of resistance through horizontal gene transfer.
There is a strong correlation between MRGs and ARGs, confirming their co-occurrence and suggesting the potential for co-selective pressure. In glacial environments, we found not only ARGs but also virulence genes (VGs), indicating that glacial ice may serve as a reservoir for pathogenic strains carrying associated genes on plasmids. Additionally, the widespread presence of genes encoding hypothetical proteins with unknown functions in the variable regions of integrons suggests they play a key role in Arctic adaptation while also posing a risk for the emergence of new resistance phenotypes. However, we did not detect typical ARGs within integron cassettes, implying that integrons may be less involved in ARG dissemination in the Arctic than previously assumed. Despite this, genetic material from various sources, including anthropogenic wastewater inputs, may mix downstream, integrating into fjords and marine ecosystems. Understanding these processes in the Arctic provides critical insights into the broader dynamics of antimicrobial resistance (AMR) and its potential for global spread, particularly in the context of the climate crisis.
Current AMR research is increasingly focused on the environmental spread of ARGs, yet significant knowledge gaps remain regarding these processes in the rapidly changing Arctic. There is also growing interest in the role of mobile genetic elements, such as plasmids and integrons, in facilitating the spread of resistance genes. Increasing human activity, pollution, and warming in the Arctic could enhance the release and spread of plasmid-related genes to the broader pool of ARGs in the Arctic Ocean. Increasing reports suggest that melting glaciers may play a role in releasing many of the previously deposited contaminants. Understanding the mechanisms behind this phenomenon, as well as identifying hotspots where gene transfer occurs, could help understand past and future environmental changes. A clearer understanding of these contemporary processes could also inform policies aimed at mitigating ARG spread, reducing resistance, and conserving ecosystems. Our research can support actions related to environmental monitoring, water quality, and waste management by integrating AMR monitoring into Arctic regions and guiding risk assessments. This research highlights the importance of studying AMR in the cryosphere, not only in the Arctic but worldwide.
Monitoring the spread of ARGs across different environmental and geological contexts is essential for raising awareness among the public, policymakers, and decision-makers about the associated risks. This is particularly critical in regions where glaciers serve as the primary freshwater source for tourism, agriculture, and domestic use. By identifying the role of mobile genetic elements in environmental resistance, our research also supports biotechnological innovations for rapid detection and continuous AMR monitoring. Additionally, it highlights the urgency of protecting remote ecosystems from pollution. These efforts align with the "One Health" framework, which promotes collaboration across health, agriculture, and environmental sectors at global, regional, and local levels to mitigate pollution and combat AMR. Key actions could include establishing international monitoring programs to track AMR spread in sensitive regions like the Arctic and implementing stricter regulations to limit pollutant emissions in these fragile ecosystems.
Figure 1. Research team. From the top left corner: Nicoletta Makowska-Zawierucha, Artur Trzebny, Krzysztof Zawierucha, Vineeth Manthapuri, James A. Bradley, Amy Pruden.