Bacterial Adhesin
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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 b ...
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 Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following ...
. Adherence is an essential step in
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
l
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
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 dis ...
, required for colonizing a new
host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County People *Jim Host (born 1937), American businessman * Michel 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 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 A tropism is a biological phenomenon, indicating growth or turning movement of a biological organism, usually a plant, in response to an environmental stimulus. In tropisms, this response is dependent on the direction of the stimulus (as oppos ...
. Adhesins are expressed by both pathogenic bacteria and saprophytic bacteria. This prevalence marks them as key microbial
virulence factor Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following ...
s 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 A pilus (Latin for 'hair'; plural: ''pili'') is a hair-like appendage found on the surface of many bacteria and archaea. The terms ''pilus'' and '' fimbria'' (Latin for 'fringe'; plural: ''fimbriae'') can be used interchangeably, although some r ...
. 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 a ...
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 X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
. 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 Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following ...
. "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 dis ...
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. 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 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 The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
is directed primarily against bacterial adhesins. Recent studies from
Worcester Polytechnic Institute Worcester Polytechnic Institute (WPI) is a Private university, private research university in Worcester, Massachusetts. Founded in 1865 in Worcester, WPI was one of the United States' first engineering and technology universities and now has 14 ac ...
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 A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...
(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 BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative ...
to the Dr
blood group A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates ...
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 respons ...
component of
decay-accelerating factor Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the ''CD55'' gene. DAF regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during ...
(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. 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. The Dr family of adhesins are particularly associated with
cystitis A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...
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 may ...
.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 gon ...
'' 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 gon ...
'' 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 infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...
s. 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.


See also

* Fungal adhesin *
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 anot ...


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