Yad fimbriae are triggered by host cues and enhance extraintestinal pathogenic Escherichia coli tissue colonisation during bloodstream infection.

Bacterial pathogens that infect host sites beyond their native ecological niche must be equipped to cope with unique challenges across distinct environments. This often manifests in the upregulation of virulence factors specifically in response to host cues, which enhance pathogen fitness. Extraintestinal pathogenic Escherichia coli (ExPEC) typically colonise the host-gut asymptomatically but can disseminate to infectious sites such as the bladder, kidneys and bloodstream. The molecular basis of urinary tract colonisation by ExPEC is well established, with adhesion via chaperone-usher fimbriae being a critical determinant. However, mechanisms that promote bloodstream infection are poorly understood. Here, we show that several ExPEC fimbriae are upregulated rapidly in response to human serum, mimicking exposure to the bloodstream environment. Yad fimbriae displayed the most significant induction in response to this host cue in two distinct ExPEC isolates, and we show that the gene cluster is prevalent across the E. coli phylogeny, suggesting a common virulence mechanism. Expression of Yad fimbriae was found to be repressed at the transcriptional level by the histone-like nucleoid structuring protein (H-NS). Furthermore, a prolonged elevation in Yad transcription was sustained throughout many generations of growth in serum, suggesting that cue(s) in the bloodstream counteract H-NS repression, triggering cell-surface expression of Yad fimbriae. Finally, Yad transcription was significantly upregulated within systemic tissue in a murine model of bacteremia and we show that deletion of the yad genes significantly attenuated ExPEC colonisation during infection. These data reveal Yad fimbriae as an important ExPEC virulence factor and support the concept of cellular adhesion as a crucial element of bacterial bloodstream pathogenesis.