How bacteria tackle metformin in the wild

Metformin is the main first-line treatment for type II diabetes, prescribed to millions of people worldwide. But have you ever wondered what happens after it’s done its job in patients?

Surprisingly, metformin and its metabolites, including guanylurea, are among the most prevalent anthropogenic chemical pollutants in wastewater globally, reaching microM concentrations. These compounds are not removed through typical wastewater treatment protocols, presenting a significant environmental concern and posing a unique challenge for microbial communities. Metformin has been shown to alter the composition of the gut microbiome and to promote the development of antibiotic resistance in E. coli. Moreover, some recent studies have isolated bacteria that utilize metformin as a nitrogen and/or carbon source, suggesting that biodegradation of metformin and guanylurea may be a viable strategy for the remediation of these compounds.

A recent study from the Randy Stockbridge Group highlighted the capability of certain bacterial transport proteins, specifically those belonging to the small multidrug resistance (SMR) family, to export metformin metabolites such as guanylurea. Researchers examined the transport kinetics and mechanisms by which SMR proteins, specifically the SMRGdx homologs, interact with and transport guanylurea. They demonstrated robust transport of guanylurea, with the same transport stoichiometry and kinetics as the physiological substrate Gdm+.

The research utilized various methodologies, including solid-supported membrane electrophysiology (SURFE2R), proteoliposome-based transport assays, and structural analysis via x-ray crystallography, to elucidate the mechanisms of substrate binding and transport across the bacterial membrane.

The emerging physiological role of the SMRGdx transporters in the export of metformin metabolites suggests a novel adaptation of microbial communities to human-influenced environments, particularly those impacted by pharmaceutical pollutants.

The findings of this study open up new avenues for addressing environmental pollution with pharmaceuticals. Understanding how bacteria can degrade or export drugs like metformin suggests potential strategies for bioremediation—using microbes to clean up polluted environments. Moreover, it highlights the need for more sustainable pharmaceutical practices that consider the lifecycle of medications and their ecological impacts.

Find the original article here: Transport of metformin metabolites by guanidinium exporters of the small multidrug resistance family

Learn more about Solid Supported Membrane-Based Electrophysiology and SURFE²R devices here: https://www.nanion.de/products/surfe2r-n1/