Cell adhesion molecules in the pathogenesis of and host defence against microbial infection

Eukaryotic cell adhesion molecules (CAMs) are used by various cells and ext racellular molecules in host defence against infection. They are involved i n many processes including recognition by circulating phagocytes of a site of inflammation, transmigration through the endothelial barrier, diapedesis through basement membrane and extracellular matrix, and release of effecto r mechanisms at the infected site. CAMs involved in leucocyte-endothelial c ell interaction include the selectins, integrins, and members of the immuno globulin superfamily. However, CAMs are also used by various microorganisms (protozoa, fungi, bacteria, and viruses) during their pathogenesis. For ex ample, bacteria that utilise CAMs include Mycobacterium tuberculosis, Liste ria monocytogenes, Yersinia spp, enteropathogenic Escherichia coil, Shigell a spp, Neisseria spp, Bordetella spp, and Borrelia burgdorferi. In addition , CAMs are involved in the pathogenetic effects of the RTX toxins of Pasteu rella haemolytica, Actinobacillus actinomycetemcomitans, and the superantig en exotoxins of Staphylococcus aureus and Streptococcus pyogenes. A recurre nt and topical theme of potential importance within the bacterial group is the intimate relation between CAMs, bacterial protein receptors, and type I II secretion systems. For example, the IpaBCD protein complex is secreted b y the type III system of Shigella flexneri and interacts with alpha(5)beta( 1) integrin on the eukaryotic cell surface, followed by Rho mediated intern alisation; this illustrates the relevance of cellular microbiology. CAMs mi ght prove to be novel therapeutic targets. Comparative genomics has provide d the knowledge of shared virulence determinants among diverse bacterial ge nera, and will continue to deepen our understanding of microbial pathogenes is, particularly in the context of the interaction of prokaryotic and eukar yotic molecules.