Global lessons from antibiotic resistance: metformin-hydrolyzing genes in transposable elements, a new threat for type II diabetic patients?

Metformin drug, widely used to treat type II diabetic patients, is a major pharmaceutical pollutant of wastewater and rivers. This environmental exposure has driven the evolution of bacteria, such asAminobacterandPseudomonas, to degrade metformin via a Ni²⁺-dependent metformin hydrolase complex (MfmAB). Here we decipher the mechanism of acquisition and horizontal transfer of themfmABgenes, initially mobilized fromAminobacterchromosomes toPseudomonasconjugative plasmids via common transposable elements (IS1182 andIS3/IS6 elements) in composite transposons, carrying also other genes involved in guanylurea and biguanides degradation (guuHandbguH). These mobile elements, historically involved in acquisition of antibiotic-resistant genes from the environment before clonal expansion in clinical settings, now threaten to co-select for both metformin-degrading and antibiotic resistance genes in contaminated waters. This represents a global threat for diabetic patients with concurrent infections that should be urgently added in the roadmap of research in the context of One Health.