Global biogeochemical cycles drive our planet’s health through the control of microbial habitats, nutrient availability and distribution, and exposure to reactive chemicals. By releasing heavy metals into the environment and altering natural fluxes, Humans have carried out a planetary wide experiment for millennia that is pushing our ecosystem towards an unknown future. More recently, this has included the production, use and release of antibiotics, which has led to the spread of antibiotic resistance genes (ARGs) across the globe. ARG spread has critical consequences for human and environmental health, however, the underlying mechanisms that led to the spread of ARGs worldwide are unknown. The presence of heavy metal resistance genes (HMRGs) and ARGs in microbial genomes suggests a co-selection.
I will combine geochemical and microbiological discovery of the links between heavy metal pollution and the spread of antimicrobial resistance from pre-industrial times to the present using paleoecological archives. I will identify the mechanisms underlying metal-induced ARG spread, the preferential relationships between specific metals and ARGs, and quantify the timing between drug/metal use and ARG spread, determine the impact of emerging pollutants on ARG spread, and evaluate the future risk of remobilization of contaminants and resistance genes. These results will provide fundamental data that can be used to inform policy on emission guidelines and on drug development.
Context and Problem: The rapid and global spread of antibiotic resistance is a critical crisis for both human and ecosystem health, projected to cause 10 million deaths annually by 2050 if left unchecked. A major unanswered question is how antibiotic resistance genes (ARGs) spread so effectively, even to pristine environments with no local antibiotic use. This project addresses a key hypothesis: heavy metal pollution is a primary, long-term driver of this spread. Human activities like mining and industry have released heavy metals into the environment for millennia, creating a persistent selective pressure on microbes. To survive, bacteria have evolved heavy metal resistance genes (HMRGs). Crucially, these HMRGs are often physically linked to ARGs on the same mobile pieces of DNA (plasmids). When metals select for bacteria carrying HMRGs, they inadvertently also select for and spread the linked ARGs, even in the absence of antibiotics. This process, known as co-selection, is believed to be a hidden engine behind the global antibiotic resistance crisis. A significant barrier to proving this has been the lack of long-term data. Current environmental studies are limited to ecosystems already polluted for decades, making it impossible to understand the historical origins and mechanisms of this relationship.
Overall Objective: This project, Paleo-MARE, aims to overcome this barrier by uncovering the historical link between heavy metal pollution and antimicrobial resistance. The core idea is to use paleo-archives—ice and sediment cores—as a time machine to analyze ancient microbial DNA (paleo-microbiomes) and trace the evolution of metal and antibiotic resistance genes from pre-industrial times to the present. By linking this genomic data with precise geochemical records of metal pollution over the last 1,000-2,000 years, the project will determine how human activity has mobilized and spread antibiotic resistance.
In summary, by deciphering the ancient and ongoing "planetary experiment" of metal pollution, Paleo-MARE aims to provide the critical evidence needed to understand, predict, and ultimately control the global spread of antimicrobial resistance, thereby tackling one of the most pressing threats to global health.
