Chemical attenuation of pilus function and assembly in Gram-negative bacteria

Bacteria express a multitude of hair-like adhesive appendages on their cell surfaces, together referred to as pili or fimbriae. In Gram-negative bacteria, these proteinaceous structures are assembled through a number of dedicated secretion pathways including the chaperone–usher pathway, the nucleation/precipitation pathway and the type IV pilus pathway. Pili are prevalent in pathogenic strains and play important roles in the establishment and persistence of bacterial infections by mediating host cell adhesion, cell invasion or biofilm formation. Their indispensible roles in pathogenesis render them attractive targets for directed therapeutic intervention. Here, we describe the recent advances in the chemical attenuation of pilus-associated virulence in Gram-negative bacteria.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (173 K)Download as PowerPoint slideHighlights► The promise of receptor analogues and biogenesis inhibitors to curb adhesive pili. ► Mannoside-based type 1 pilus inhibitors are effective against UPEC in a murine model of UTI. ► Pilus adhesins contain specificity and affinity-determining regions. ► Bi-cyclic 2-pyridones inhibit curli and chaperone–usher pilus biogenesis.