Adhesins are cell-surface components or appendages of bacteria that facilitate
adhesion
Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another).
The forces that cause adhesion and cohesion can ...
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
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
l
pathogenesis or
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
, required for
colonizing a new
host.
Adhesion and bacterial adhesins are also a potential target for prophylaxis or treatment of bacterial infections.
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
The lacrimal canaliculi, (sing. canaliculus), are the small channels in each eyelid that drain lacrimal fluid, from the lacrimal puncta to the lacrimal sac. This forms part of the lacrimal apparatus that drains lacrimal fluid from the surface of ...
tissues in mammals, or even tooth enamel.
Most
fimbria of
gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
bacteria function as adhesins, but in many cases it is a minor subunit
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
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.
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
fimbria or
pilus.
The bacterial adhesion consists primarily of an intramembranous structural protein which provides a scaffold upon which several extracellular adhesins may be attached.
However, as in the case of the CFA1 fimbriae, the structural protein itself can sometimes act as an adhesion if a portion of the protein extends into the
ECM.
FimH adhesin—structure
The best characterized bacterial adhesin is the type 1 fimbrial FimH adhesin. This adhesin is responsible for
D-mannose sensitive adhesion.
The bacterium synthesizes a precursor protein consisting of 300
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s then processes the protein by removing several signal peptides ultimately leaving a 279 amino acid protein.
Mature FimH is displayed on the bacterial surface as a component of the type 1 fimbrial organelle.
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.
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.
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.
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."
Many bacterial pathogens are able to express an array of different adhesins. Expression of these adhesins at different phases during
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
play the most important role in adhesion based virulence.
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
vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. s comes from early studies which indicated that an important component of protective immunity against certain bacteria came from an ability to prevent adhesin binding.
Additionally, Adhesins are attractive
vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. candidates because they are often essential to infection and are surface-located, making them readily accessible to
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
.
The effectiveness of anti-adhesin
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
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
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
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.
Recent studies from
Worcester Polytechnic Institute show that the consumption of
cranberry juice
Cranberry juice is the liquid juice of the cranberry, typically manufactured to contain sugar, water, and other fruit juices. Cranberry – a fruit native to North America – is recognized for its bright red color, tart taste, and versat ...
may inhibit the action of UPEC adhesins. Using
atomic force microscopy researchers have shown that adhesion forces decrease with time following
cranberry juice
Cranberry juice is the liquid juice of the cranberry, typically manufactured to contain sugar, water, and other fruit juices. Cranberry – a fruit native to North America – is recognized for its bright red color, tart taste, and versat ...
consumption.
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.
Finally, many adhesins present as different immunologically distinct antigenic varieties, even within the same
clone (as is the case in ''
Neisseria gonorrhoeae'').
Despite these challenges, progress is being made in the creation of anti-adhesion vaccines. In animal models,
passive immunization Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when ...
with anti FimH-antibodies and vaccination with the
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
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.
Specific examples
Dr family
The Dr family of adhesins
bind to the Dr
blood group antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
component of
decay-accelerating factor (DAF).
[ These ]protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s contain both fimbriated and afimbriated adherence structures and mediate adherence of uropathogenic ''Escherichia coli'' to the urinary tract. They do so by inducing the development of long cellular extensions that wrap around the bacteria.[ They also confer the mannose-resistant hemaglutination phenotype, which can be inhibited by ]chloramphenicol
Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, chole ...
. The N-terminal portion of the mature protein is thought to be responsible for chloramphenicol sensitivity. Also, they induce activation of several signal transduction cascades, including activation of PI-3 kinase
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which ...
.
The Dr family of adhesins are particularly associated with cystitis and pregnancy-associated pyelonephritis
Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications ...
.[Identified Virulence Factors of UPEC : Adherence]
State Key Laboratory for Moleclular Virology and Genetic Engineering, Beijing. Retrieved July 2011
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''. 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.
''N. gonorroheae''
''N. gonorrhoeae
''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular), or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria isolated by Albert Neisser in 1879. It causes the sexually transmitted genitourinary infection g ...
'' is host restricted almost entirely to humans. "Extensive studies have established type 4 fimbrial adhesins of ''N. gonorrhoeae
''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular), or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria isolated by Albert Neisser in 1879. It causes the sexually transmitted genitourinary infection g ...
'' virulence factors." These studies have shown that only strains capable of expressing fimbriae are pathogenic. High survival of polymorphonuclear neutrophils (PMNs) characterizes ''Neisseria gonorrhoeae'' infections. Additionally, recent studies out of Stockholm have shown that ''Neisseria'' can hitchhike on PMNs using their adhesin pili thus hiding them from neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
phagocytic activity. This action facilitates the spread of the pathogen throughout the epithelial cell layer.
''E. coli''
''Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' 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
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
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.
See also
* Fungal adhesin
Fungal adhesins are proteins located on the surface of fungal cells, specifically found on the outside of the cell wall. They allow fungi to colonize various substrates and to bind to host tissues. Adhesion to tissue is an obligatory first step i ...
* Trimeric autotransporter adhesins (TAA)
In molecular biology, trimeric autotransporter adhesins (TAAs), are proteins found on the outer membrane of Gram-negative bacteria. Bacteria use TAAs in order to infect their host cells via a process called cell adhesion. TAAs also go by ano ...
References
Adhesins are also used in cell communication, and bind to surface communicators. Can also be used to bind to other bacteria.
External links
*
{{DEFAULTSORT:Bacterial Adhesin
Bacteriology
Virulence factors