Bacterial adhesin
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.[1] Adhesion and bacterial adhesins are also a potential target either for prophylaxis or for the treatment of bacterial infections.[2]
Background
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.[3]
Most
Bacterial adhesins provide species and tissue
Structures
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
FimH adhesin—structure
The best characterized bacterial adhesin is the type 1 fimbrial FimH adhesin. This adhesin is responsible for D-mannose sensitive adhesion.[3] The bacterium synthesizes a precursor protein consisting of 300 amino acids then processes the protein by removing several signal peptides ultimately leaving a 279 amino acid protein.[3] Mature FimH is displayed on the bacterial surface as a component of the type 1 fimbrial organelle.[3]
In 1999, the structure of FimH was resolved via x-ray crystallography. FimH is folded into two domains. The N terminal adhesive domain plays the main role in surface recognition while the C-terminal domain is responsible for organelle integration.[5] 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.[5] This basic structure is conserved across type 1 fimbrial adhesins though recent studies have shown that in vitro induced mutations can lead to the addition of C-terminal domain specificity resulting in a bacterial adhesion with dual bending sites and related binding phenotypes.[6]
As virulence factors
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."[3] Many bacterial pathogens are able to express an array of different adhesins. Expression of these adhesins at different phases during infection play the most important role in adhesion based virulence.[3] Numerous studies have shown that inhibiting a single adhesin in this coordinated effort can often be enough to make a pathogenic bacterium non-virulent. This has led to the exploration of adhesin activity interruption as a method of bacterial infection treatment.
Vaccines based on adhesins
The study of adhesins as a point of exploitation for vaccines comes from early studies which indicated that an important component of protective immunity against certain bacteria came from an ability to prevent adhesin binding.[7] 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
Recent studies from Worcester Polytechnic Institute show that the consumption of cranberry juice may inhibit the action of UPEC adhesins. Using atomic force microscopy researchers have shown that adhesion forces decrease with time following cranberry juice consumption.[8] 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.[3] Finally, many adhesins present as different immunologically distinct antigenic varieties, even within the same clone (as is the case in Neisseria gonorrhoeae).[9]
Despite these challenges, progress is being made in the creation of anti-adhesion vaccines. In animal models,
Specific examples
Dr family
Adhesin_Dr | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | Adhesin_Dr | ||||||||
Pfam | PF04619 | ||||||||
Pfam clan | CL0204 | ||||||||
InterPro | IPR006713 | ||||||||
|
The Dr family of adhesins
The Dr family of adhesins are particularly associated with
Multivalent Adhesion Molecules
Multivalent Adhesion Molecules (MAMs) are a widespread family of adhesins found in Gram negative bacteria, including E. coli, Vibrio, Yersinia, and Pseudomonas aeruginosa.[15] MAMs contain tandem repeats of mammalian cell entry (MCE) domains which specifically bind to extracellular matrix proteins and anionic lipids on host tissues. Since they are abundant in many pathogens of clinical importance, Multivalent Adhesion Molecules are a potential target for prophylactic or therapeutic anti-infectives. The use of a MAM targeting adhesion inhibitor was shown to significantly decrease the colonization of burn wounds by multidrug resistant Pseudomonas aeruginosa in rats.[16]
N. gonorroheae
E. coli
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.[18] to attach to the intestinal lining. Additionally, UPEC causes about 90% of urinary tract infections.[19] 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.[19] By studying this particular adhesion, researchers hope to develop adhesion-specific vaccines which may serve as a model for antibody-mediation of pathogen adhesion.[19]
See also
References
- PMID 12629063.
- PMID 23799663.
- ^ PMID 11043979.
- PMID 19527885.
- ^ PMID 10446051.
- PMID 9572927.
- ISBN 978-0849348945.
- PMID 21480803.
- ISBN 978-0849348945.
- PMID 10669375.
- PMID 9110982.
- ^ a b c d Identified Virulence Factors of UPEC : Adherence, State Key Laboratory for Moleclular Virology and Genetic Engineering, Beijing. Retrieved July 2011
- PMID 9169726.
- PMID 1670929.
- PMID 21709226.
- PMID 27996032.
- PMID 21949708.
- ^
Gaastra W, de Graaf FK (June 1982). "Host-specific fimbrial adhesins of noninvasive enterotoxigenic Escherichia coli strains". Microbiol. Rev. 46 (2): 129–61. PMID 6126799.
- ^ PMID 21768279.
Adhesins are also used in cell communication, and bind to surface communicators. Can also be used to bind to other bacteria.
External links
- Bacterial+Adhesin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)