Biogenesis and Functionality of Sortase-Assembled Pili in Gram-Positive Bacteria

A unique class of multimeric proteins made of covalently linked subunits known as pili, or fimbriae, are assembled and displayed on the gram-positive bacterial cell surface by a conserved transpeptidase enzyme named pilus-specific sortase. Sortase-assembled pili are produced by a wide range of gram-positive commensal and pathogenic bacteria inhabiting diverse niches such as the human oral cavity, gut, urogenital tract, and skin. These surface appendages serve many functions, including as molecular adhesins, immuno-modulators, and virulence determinants, that significantly contribute to both the commensal and pathogenic attributes of producer microbes. Intensive genetic, biochemical, physiological, and structural studies have been devoted to unveiling the assembly mechanism and functions, as well as the utility of these proteins in vaccine development and other biotechnological applications. We provide a comprehensive review of these topics and discuss the current status and future prospects of the field.