The majority of bacteria which colonize humans display sharp host and tissue tropisms; consequently, relatively little is known about how they initiate colonization on mucosal surfaces. The mouth has a variety of features which have enabled it to serve as a useful model for the discovery of basic principles of host-parasite interactions occurring in mucosal environments. Early studies demonstrated that indigenous bacteria attach to surfaces of the mouth in a highly selective manner; attachment was often observed to correlate with colonization. These studies led to the recognition that bacterial attachment is an essential step for colonization in environments which contain surfaces exposed to a fluid flow. Bacterial adhesion has subsequently grown into a major area of infectious disease research. Many bacteria have been found to possess proteinaceous components, called "adhesins", on their surfaces which bind in a stereochemically specific manner to complementary molecules, or "receptors", on the tissue surface. Adhesins are often lectins which bind to saccharide receptors, but some adhesins are thought to bind to proteinaceous receptors. Studies of components of human saliva, which adsorb to hydroxyapatite (HA) surfaces similar to those of teeth, and promote the attachment of prominent plaque bacteria, have revealed that the acidic proline-rich proteins (PRPs) promote the attachment of several important bacteria. These include strains of Actinomyces viscosus, Bacteroides gingivalis, some strains of Streptococcus mutans, and others. The salivary PRP's are a unique family of molecules. However, segments of PRPs are structurally related to collagen. This may be significant, since B. gingivalis and certain cariogenic streptococci bind to collagenous substrata, and such interactions may facilitate their invasion into gingival tissues, or into dentin or cementum, respectively. Another unexpected observation was that although A. viscosus and other bacteria bind avidly to PRPs adsorbed onto apatitic surfaces, they do not interact with PRPs in solution. PRP molecules evidently undergo a conformational change when they adsorb to HA, and adhesins of A. viscosus recognize cryptic segments which are only exposed in adsorbed molecules. This provides the bacteria with a mechanism for efficiently attaching to teeth while suspended in saliva. It also offers a molecular explanation for their sharp tropisms for human teeth. It has proven convenient to refer to such hidden receptors for bacterial adhesins as "cryptitopes" (from cryptic, meaning hidden, and topo, meaning place).(ABSTRACT TRUNCATED AT 400 WORDS)