Бактериальные адгезины: структура, функции и роль в патогенезе.

Adhesins are cell surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor. Adherence is an essential step in bacterial pathogenesis or infection, required for colonizing a new host. Adhesion and bacterial adhesins are also a potential target either for prophylaxis or for the treatment of bacterial infections.

Bacteria are typically found attached to and living in close association with surfaces. During the bacterial lifespan, a bacterium is subjected to frequent shear forces. In the crudest sense, bacterial adhesins serve as anchors allowing bacteria to overcome these environmental shear forces, thus remaining in their desired environment. However, bacterial adhesins do not serve as a sort of universal bacterial Velcro. Rather, they act as specific surface recognition molecules, allowing the targeting of a particular bacterium to a particular surface such as root tissue in plants, lacrimal duct tissues in mammals, or even tooth enamel. Most fimbria of gram negative bacteria function as adhesins, but in many cases it is a minor subunit protein at the tip of the fimbriae that is the actual adhesin. In gram positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. To effectively achieve adherence to host surfaces, many bacteria produce multiple adherence factors called adhesins. Bacterial adhesins provide species and tissue tropism. Adhesins are expressed by both pathogenic bacteria and saprophytic bacteria. This prevalence marks them as key microbial virulence factors in addition to a bacterium's ability to produce toxins and resist the immune defenses of the host.

Through the mechanisms of evolution, different species of bacteria have developed different solutions to the problem of attaching receptor specific proteins to the bacteria surface. Today many different types and subclasses of bacterial adhesins may be observed in the literature. The typical structure of a bacterial adhesion is that of a fimbria or pilus. A tetra peptide loop links the two domains. Additionally, a carbohydrate binding pocket has been identified at the tip of the N terminal adhesive domain.

The majority of bacterial pathogens exploit specific adhesion to host cells as their main virulence factor. "A large number of bacterial adhesins with individual receptor specificities have been identified." Additionally, Adhesins are attractive vaccine candidates because they are often essential to infection and are surface located, making them readily accessible to antibodies. The effectiveness of anti adhesin antibodies is illustrated by studies with FimH, the adhesin of uropathogenic Escherichia coli (UPEC). Work with E. coli stems from observations of human acquired immunity. Children in third world countries may suffer from several episodes of E. coli associated diarrhea during the first three years of life. If the child survives this initial period of susceptibility, infection rates typically drop substantially. Field studies show that this acquired immunity is directed primarily against bacterial adhesins. This research has opened the door to further exploration of orally administered vaccines which exploit bacterial adhesins. A number of problems create challenges for the researcher exploring the anti adhesin immunity concept. First, a large number of different bacterial adhesins target the same human tissues. Further, an individual bacterium can produce multiple different types of adhesin, at different times, in different places, and in response to different environmental triggers. Despite these challenges, progress is being made in the creation of anti adhesion vaccines. In animal models, passive immunization with anti FimH antibodies and vaccination with the protein significantly reduced colonization by UPEC. Moreover, the Bordetella pertussis adhesins FHA and pertactin are components of three of the four acellular pertussis vaccines currently licensed for use in the U. S. Additionally, anti adhesion vaccines are being explored as a solution to urinary tract infection (UTIs). The use of synthetic FimH adhesion peptides was shown to prevent urogenital mucosal infection by E. coli in mice.

N. gonorrhoeae is host restricted almost entirely to humans.

Escherichia coli strains most known for causing diarrhea can be found in the intestinal tissue of pigs and humans where they express the K88 and CFA1. to attach to the intestinal lining. Additionally, UPEC causes about 90% of urinary tract infections. Of those E. coli which cause UTIs, 95% express type 1 fimbriae. FimH in E. coli overcomes the antibody based immune response by natural conversion from the high to the low affinity state. Through this conversion, FimH adhesion may shed the antibodies bound to it. Escherichia coli FimH provides an example of conformation specific immune response which enhances impact on the protein. By studying this particular adhesion, researchers hope to develop adhesion specific vaccines which may serve as a model for antibody mediation of pathogen adhesion.