Alternative Strategies for Becoming an Insider Lessons from the Bacterial World

ers such as the intestinal epithelium and the placental and blood-brain barriers. It is thought that the ability of these bacteria to invade non-phagocytic cells plays an essential role in breaching those natural barriers. Efforts to identify L. monocytogenes determinants that mediate internalization resulted in the characterization of two related proteins, InlA, also known as internalin, and InlB (Cossart and Lecuit, 1998). InlA is required for L. mono-Many microbial pathogens that have sustained long-cytogenes entry into the enterocyte-like intestinal epi-standing associations with their vertebrate hosts have thelial cell Caco-2, while InlB mediates entry into hepato-evolved sophisticated strategies to subvert cellular cytes and several endothelial, epithelial, and fibroblast-functions. These strategies are not accidental but rather like cell lines. Both these proteins are able to mediate the result of evolutionary forces operating over extended the internalization of coated latex beads, indicating that periods of time to secure the survival of both the patho-they are not only necessary, but also sufficient to trigger gen and the host. Therefore, it should not come as a bacterial internalization. InlA and InlB share significant surprise that our developing understanding of patho-amino acid sequence similarity and belong to a Listeria gen/host cell interactions is not only uncovering won-protein family with at least five additional members. A derful biology but also teaching us useful lessons about common feature of this protein family is the presence the inner workings of the cell. at their amino terminus of a domain composed of a An essential step in the life cycle of many important varying number of leucine-rich repeats (LRRs). This do-pathogenic bacteria is their ability to invade cells that main is critical for the stimulation of bacterial entry. It are normally nonphagocytic. Gaining access to an intra-has been proposed that the composition and number cellular niche provides bacteria with an environment of the LRRs establishes the receptor specificity of these permissive for growth, allows them to avoid host de-bacterial ligands which, in turn, determines their individ-fense mechanisms, or permits them to gain access to ual contribution to bacterial entry into different mamma-deeper tissues. Although certain cells such as macro-lian cells. Recently, the x-ray crystal structure of the phages are able to internalize particles of the size of leucine-rich repeats domain of InlB was solved, reveal-a bacterium, gaining access into nonphagocytic cells ing intriguing features (Marino et al., 1999). The LRRs requires very specific adaptations. The mechanisms by are arranged in …