Fimbrial surface display systems in bacteria: from vaccines to random libraries.

The double membrane system of Gram-negative bacteria is an efficient barrier instrumental in maintaining a steady environment in the cytoplasm. Only a few lowmolecular-mass substances are able to cross this barrier unassisted from the cell exterior. On the other hand, the Gram-negative cell envelope also constitutes a formidable obstacle for proteins destined for the cell exterior. Gram-negative bacteria have developed various systems for protein export to the cell exterior ; four major systems can be distinguished (Lory, 1998). By these systems a wide range of proteins can be routed to the surface, and many of these remain physically attached to and displayed on the cell surface. Such proteins are key players in a number of natural processes, such as adhesion, colonization of target surfaces, biofilm formation, motility, signal transduction, enzymic degradations, etc. However, many proteins of interest in medicine and biotechnology are not surface-displayed and}or not of bacterial origin. An attractive way to obtain surface display of such proteins or sectors thereof is to graft them into permissible positions on a naturally occurring bacterial surface protein and express the chimeric protein on the cell surface. Surface display of heterologous proteins on bacteria has resulted in a number of applications, such as recombinant vaccines, reagents for diagnostics, whole-cell biocatalysts and bioadsorbants, and systems for scanning peptide libraries (Georgiou et al., 1997).