Horizontal Gene Transfer at Landscape Scale in Microbial Communities Under Selection For Antimicrobial Resistance

This project will study the spread of the genes that make bacteria resistant to antibiotics, and how that spread is affected by heavy metal pollution. One of the greatest threats facing human society in the coming decades is an increase in antimicrobial resistant bacteria. The widespread use of antibiotics starting in the mid-20th century led to plummeting rates of mortality from infections and contributed to one of the greatest increases in life expectancy of any technological innovation.

Unfortunately more and more infections that resist antibiotic treatment are occurring, threatening to undo those advances and usher in a much more dangerous post-antibiotic era. The overuse of antibiotics by doctors and hospitals is often cited as the cause of this change, but research suggests that environmental pollution might also play a role. In a historically contaminated part of Birmingham, Alabama, that has housed coal-burning facilities for over a century, elevated levels of heavy metals like lead and manganese appear to favor the evolution of bacteria that are resistant not only to these toxic substance but also to antibiotics.

The predominantly African American residents of the affected neighborhoods already face elevated levels of respiratory and other chronic diseases, and they may also face elevated risk of dangerous antibiotic resistant infection due to the heavy metals in their environment. This research will put a scientific lens on the question of where antibiotic resistance comes from and how it spreads from point sources into the environment, but it will also confront the environmental injustice experienced by the human beings who are bearing the costs of decades of industrial pollution.

The project will involve the people who live in the affected neighborhoods, where the researchers will attempt to win back some of the trust in science that has been lost due to a history of neglect and corruption surrounding this neighborhood and its ongoing struggle with the residue of its industrial past.

It is generally accepted that antibiotic resistance spreads fastest in bacteria through horizontal gene transfer. This research will attempt to observe these exchanges taking place using a unique laboratory method, where an environmental sample is separated from laboratory bacteria by a membrane that has pores big enough to allow DNA, but not cells, to pass, and then to see what kinds of antibiotic resistance genes from the environment are able to be transferred into the lab strains.

Researchers will also collect soil and wastewater from around the Birmingham area to see how much antibiotic resistance exists in the environment, and mathematicians will use computer models to understand whether the resistance genes are coming from humans using antibiotics as medicine, from agricultural sources, from pollution in the soil, or from a combination of these factors. Despite the critical importance of horizontal gene transfer in this and other bacterial activities, very little is known about how it actually takes place in nature, how fast it can move genes around, or how far from a point source it can move resistance genes; this research will address all of these topics using cutting-edge laboratory and computational tools.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.