Molecular Mechanisms Of Invasion Research Articles

Molecular mechanisms of invasion by Entamoeba histolytica

Amebiasis is the third leading cause of death due to parasitic disease. Adherence to and contact-dependent killing of host cells requires the galactose-inhibitable lectin, a heterodimeric glycoprotein composed of heavy and light subunits. The cysteine-rich extracellular domain of the heavy subunits has identity with β1 integrins, complement receptor CD59, and complement components C8 and C9; the light subunit sequence is unlike any other sequenced protein. Monoclonal antibodies to the cysteine-rich domain identify pathogenic-specific domains, have adherence-inhibitory and -enhancing properties, block contact-dependent cytotoxicity, and abrogate complement C5b-9 resistance. The purified lectin has galactose-binding activity and confers C5b-9 resistance to susceptible amebae. The accumulated evidence points to the same cell surface galactose-inhibitable lectin as a mediator of two activities required for invasion: adherence and complement resistance.

Microbial invasion: a covert activity?

In contrast to nonpathogenic microorganisms that exist happily in biofilms on various organic and inorganic surfaces, many pathogenic microbes have the additional ability to invade host tissues by inducing their own endocytosis and transport across normally protective barriers. This phenomenon, designated "parasite-directed endocytosis," has been observed with a variety of surfaces (intestinal, genital, nasopharyngeal, and tracheal epithelium) as well as in endothelial cells. The mechanisms involved in invasion may involve a single factor as described for some species of Yersinia, or may require multiple factors as observed in Shigellae. For the majority of pathogens, the molecular mechanisms of invasion are not well understood (e.g., Neisseria gonorrhoeae). Because parasite-directed endocytosis is reminiscent of receptor-mediated endocytosis, it is quite possible that some pathogens engage in biologic mimicry by producing a molecule that resembles a natural host ligand, for which there is a host cell receptor. Such a masquerade may allow some microbes to enter the host's inner sanctum covertly in a manner analogous to the Trojan horse, rather than overtly by destroying the mucosa and entering host tissues directly. Whereas this hypothesis is speculative at present, bacteria that produce molecules resembling insulin, calmodulin, and chorionic gonadotropin have been described.