The rise of multidrug-resistant pathogens has become a global health concern. One notable pathogen is Escherichia coli ST131, a lineage that is responsible for million cases of urinary tract infections (UTIs) annually (1). UTIs occur via the ascending route through the urethra, mostly by residential gut E. coli crossing the physical barrier. Before the pandemic ST131 lineage emerged, UTIs were mostly treatable with antibiotics. However, with resistance to almost all frontline antibiotics, ST131-associated UTIs have become difficult to treat and life-threatening, imposing a huge burden to resource-drained public healthcare (2). Worryingly, we present recent data that certain strains within the ST131 lineage have evolved mechanisms for enhanced transmission by acquiring genes that allow them to be pathogenic also inside of the gut, using both cell line and mouse infection models. These strains represent a significant public health threat and further research on their pathogenesis is warranted.