molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, trimeric autotransporter adhesins (TAAs), are proteins found on the outer membrane 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 wall ...

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 among ...

. Bacteria use TAAs in order to infect their

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 ...

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

via a process called

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

. TAAs also go by another name,

oligomeric In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...

coiled-coil A coiled coil is a structural motif in proteins in which 2–7 alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...

adhesins 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 essent ...

, which is shortened to OCAs. In essence, they are

virulence factors 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 ...

, factors that make the bacteria harmful and infective to the host

organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...

. TAAs are just one of many methods bacteria use to infect their hosts, infection resulting in diseases such as

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

, and

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

. Most bacteria infect their host through a method named the

secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...

pathway. TAAs are part of the

pathway, to be more specific the type Vc secretion system. Trimeric autotransporter adhesins have a unique structure. The structure they hold is crucial to their function. They all appear to have a head-stalk-anchor structure. Each TAA is made up of three identical proteins, hence the name trimeric. Once the membrane anchor has been inserted into the outer membrane, the passenger domain passes through it into the host extracellular environment autonomously, hence the description of autotransporter. The head domain, once assembled, then adheres to an element of the host

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

, for example,

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

, etc.

Molecular structure

Most TAAs have a similar protein structure. When observed with

electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...

, the structure has been described as a "lollipop" shape consisting of an

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

head domain, a stalk domain, and a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

membrane anchor domain. Often, the literature refers to these as Passenger domain, containing the N-terminal, head, neck, and

stalk, and the Translocation domain, referring to the C-terminal membrane anchor. Although all TAAs carry a membrane anchor in common, they may not all contain both a stalk and a head as well. In addition, all membrane anchor domains are of the left-handed parallel beta-roll type. Lupasfig2

Extended Signal Peptide Region domain

The Extended Signal Peptide Region (ESPR) is found in the N-terminus of the signal peptides of proteins belonging to the Type V secretion systems. The function of the ESPR is to aid inner membrane translocation by acting as a temporary tether. This prevents the accumulation of misfolded proteins. The ESPR can be divided into individual regions, they are as follows: N1 (charged), H1 (

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...

), N2, H2 and C ( cleavage site) domains. N1 and H1 form the ESPR and have strong

conservation Conservation is the preservation or efficient use of resources, or the conservation of various quantities under physical laws. Conservation may also refer to: Environment and natural resources * Nature conservation, the protection and manageme ...

. Function: There are several roles that the Extended Signal Peptide Region is thought to hold. First, biogenesis of proteins in the Type V Secretion System (T5SS). Second, it is thought to target the protein to the inner membrane to be translocated either by the signal recognition particle pathway (SRP) or by twin

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

translocated (TAT). Third, it has been observed and believed to regulate the rate of protein migration into the

periplasm The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found that ...

N-terminal head domain

Structure: This particular domain is a trimer of single-stranded, left-handed beta-helices. These associate to form a nine-coiled left-handed beta-roll. It contains sequence motifs, of which there is a strong similarity with other TAA heads. This indicates that there is a lot of similarity when comparing protein structure. The head domain is connected to the stalk by a short, highly conserved sequence, which is often called the neck, or occasionally named the connector. Function: The function of this protein domain is to bind to the

of the host, most notably

, and

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...

. The head domain is very important for attachment to the host cell and for

autoagglutination In hematology, red cell agglutination or autoagglutination is a phenomenon in which red blood cells clump together, forming aggregates. It is caused by the surface of the red cells being coated with antibodies. This often occurs in cold agglutini ...

, sticking to itself. Edwardsfig5

There are several types of head domain. Each domain helps the head to bind to a different component of the extracellular matrix. These are as follows: YadA-like head domain, Trp-ring, GIN, FxG, HIN1, and HIN2. This entry focuses on the first three mentioned.

YadA-like head

YadA-like head is composed of single-stranded, left-handed beta-helices, which associate further to create a nine-coiled left-handed parallel beta-roll (LPBR). It is the tightest beta-roll structure known, and the first to be discovered. The YadA head domain has eight repeat motifs, each fourteen residues in length.

Trp ring

The Trp ring is the second-most-common TAA head. Trp is an

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 am ...

named

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

. The Trp ring obtains its name from the high levels of

found in the C-terminal part of the Head domain. These work by stabilising the transition between the coiled-coil and the beta-meander where the head meets the neck or stalk. In many cases, the Trp ring is often followed by the GIN domain.

GIN

The GIN domain is a head domain named after its sequence motif GIN (

Glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

Isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...

Asparagine Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

) motif. It has an all-beta structure, whereby the two pairs of antiparallel

beta sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...

s are connected by a diagonally running extended beta-sheet. The sheets then further fold to form a beta prism in which each wall is composed of a complete set of five beta-strands. The GIN domain is often followed by a neck domain.

Neck domain

Structure: The neck domain is a homotrimer, where three of the same subunits associate. All three subunits are arranged in such a way that they resemble a "safety pin"-like structure. Function: The function of the neck domain is to be the adaptor between the larger diameter of the beta-helices and the smaller one of the coiled coil. Furthermore, just like its safety pin structure, it also has a function of pinning all three monomers together and pins it to the head domain. This increases the stability of the neck domain. There are seven different type of neck domains. They are as follows: ISneck1, ISneck2, HANS connector, DALL-1, DALL-2, DALL-3, and the neck domain. This entry focuses on the ISneck domain.

ISneck domain

The ISneck domain is a type of neck domain. There are two types of ISneck domain. This first is an ISneck which is interrupted by an insertion. The insertion can take form of either folded (ISneck 1) or much shorter, unfolded (ISneck 2) perturbation.

Stalk domain

Structure: These domains are fibrous and found in highly repetitive numbers. They contain coiled coils and their length tends to vary among different species. The coiled-coil segments of the stalk domains have two unusual properties: ::# they alternate from right-handed to left-handed

supercoiling DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a st ...

::# often interrupted by small globular domains, which owes to their appearance of segmented ropes. Furthermore, the stalk is made up entirely of pentadecads. Hence, the stalk domains can be considered

alpha helical The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

s that deviate from the standard model due to their unusual properties. From a deeper structural perspective, coiled-coil arranges itself in such a way that the crossing angle between the helices is almost zero. The packing of these helices follows a "knobs-into-holes" arrangement whereby

residues protrude forming knobs that pack into cavities formed by other residues on another helix. Then, once the knobs are packed into cavities, the three helices are wound in register around each other, so all of the residues in certain positions are at the same height. Function: Their role is to act as spacers by moving the head domains away from the bacterial cell surface and toward the

of the

. They also have a role in protecting the bacterial cell against host defences. They do this by aiding

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...

resistance. The stalk protein domain is also alternatively named the internal passenger domain. There are two types of stalk domain: the FGG domain and the right-handed stalk domain.

C-terminal membrane anchor domain

Structure: The structure of this protein domain is a left-handed coiled-coil followed by four transmembrane

beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

s. It is thought that, once trimerisation has occurred, these beta strands further fold into a 12-stranded

beta-barrel In protein structures, a beta barrel is a beta sheet composed of tandem repeats that twists and coils to form a closed toroidal structure in which the first strand is bonded to the last strand (hydrogen bond). Beta-strands in many beta-barrels are ...

. It also contains a recognition site for signal peptidases, which means the enzyme will recognise the signal peptide and cleave it at a particular point. Function: The function of th
membrane anchor domain
is to aid the movement of the

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

chain through the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

, a process known as autotransport activity. The way TAAs translocate across the outer membrane remains to be elucidated, but it is thought that it translocates inside the

, leading to transportation of the passenger domain from the C terminus to the N terminus through the beta-barrel lumen. In essence, the beta-barrel is a porin that sits within the

bacterial outer membrane The bacterial outer membrane is found in gram-negative bacteria. Its composition is distinct from that of the inner cytoplasmic cell membrane - among other things, the outer leaflet of the outer membrane of many gram-negative bacteria includes ...

. The passenger domain or in other words coiled-coil stalk domain translocates through this pore. Additional functions of the membrane anchor is to oligomerise the stalk domain and to anchor the whole protein to the

Model proteins

All Trimeric Autotransporter Adhesins are crucial virulence factors that cause serious disease in humans. The most-studied and well-known Trimeric Autotransporter Adhesins are listed below: *

YadA Yada (written: 矢田 or 谷田) is a Japanese surname. Notable people with the surname include: *Akiko Yada (born 1978), Japanese actress *Asahi Yada (born 1991), Japanese footballer *, Japanese high jumper *Kōji Yada (born 1933), Japanese voice ...

of ''

Yersinia enterocolitica ''Yersinia enterocolitica'' is a Gram-negative, bacillus-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29° C (72–84 °F), but becomes nonmotile at normal human body temperature. ''Y. enterocolitic ...

'' * NadA of ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a ...

'' * UspA1 and A2 of ''

Moraxella catarrhalis ''Moraxella catarrhalis'' is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the infec ...

'' * Hia and Hsf of ''

Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria ...

'' * BadA of ''

Bartonella henselae ''Bartonella henselae'', formerly ''Rochalimæa henselae'', is a bacterium that is the causative agent of cat-scratch disease ( bartonellosis). ''Bartonella henselae'' is a member of the genus ''Bartonella'', one of the most common types of bacte ...

YadA protein

is a protein domain found in Gram-negative bacteria such as ''

Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of ''Ye ...

'' ''enterocolitica'', ''Yersinia pestis'', and ''Yersinia pseudotuberculosis''. YadA stands for ''Yersinia'' adhesin protein A. This protein domain is an example of Trimeric Autotransporter Adhesins, and it was the first TAA to be discovered. Like other TAAs, YadA also undergoes homotrimerisation to form a stable

-binding protein. Homotrimerisation is a process whereby three of the same subunits, associate to make a complex of three identical YadA proteins. Furthermore, just like other TAAs, it has a head-stalk-anchor protein architecture. The majority of TAAs share strong similarity in the C-terminal membrane anchor region, the only member to differ across TAAs is the head, neck, and stalk regions. The head region of YadA is composed of beta-helices further folded to create a nine-coiled left-handed parallel beta-roll (LPBR).

NadA protein

Another example of a TAA is the NadA protein. The NadA protein is found in a species of Gram-negative bacteria called ''Neisseria meningitidis'', which causes

and

in humans. Studies have shown that the globular N-terminal head domain of NadA is vital for adhesion. NadA also contains a coiled-coil region and also a C-terminal membrane anchor.

UspA1 protein

UspA1 is another example of a Trimeric Autotransporter Adhesin found in the bacterium ''Moraxella catarrhalis'', found as a common cause of

middle ear The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear). The mammalian middle ear contains three ossicles, which transfer the vibrations of the eardrum into waves in the ...

infections in humans. The structure of UspA1 also has a head domain at N-terminal domain, however it is folded into the beta propeller. Like the other TAAs, it has a coiled-coil stalk region but, in this case it is extended, and it has the TAA typical C-terminal beta barrel membrane anchor domain.

Hia protein

The Hia protein is a TAA found on the outer membrane of the bacterium ''Haemophilus influenzae''. It adheres to the

respiratory epithelium Respiratory epithelium, or airway epithelium, is a type of ciliated columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways. It is not present in the vocal cords o ...

in humans. This protein can cause

and some strains cause

and

. Hia has a slightly unusual N-terminal head made of beta-prisms. The beta-prism is an unusual type of protein architecture first described by Chothia and Murzin. As the name suggests, it holds three

beta sheets The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

arranged in a triangular prism and contains internal symmetry. Additionally, the head domain contains 5 Trp-Ring domains. Furthermore, this protein also contains three neck domains, of which two are IsNeck domains in addition to other domains such as KG, GANG, and TTT domains. It also contains a coiled-coil stalk and the typically conserved TAA C terminal membrane anchor.

BadA protein

The BadA protein is another example of a TAA found in ''Bartonella henselae'' bacteria. ''Bartonella henselae'' is the causative agent of

cat scratch disease Cat-scratch disease (CSD) or felinosis is an infectious disease that most often results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People m ...

, a normally harmless disease, but, in people with a weakened

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, such as those undergoing

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

or fighting

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...

, it is more serious as it can lead to

bacillary angiomatosis Bacillary angiomatosis (BA) is a form of angiomatosis associated with bacteria of the genus ''Bartonella''. Symptoms Cutaneous BA is characterised by the presence of lesions on or under the skin. Appearing in numbers from one to hundreds, these le ...

. This a condition where

benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...

tumours A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of the

blood vessels The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

undergo uncontrolled proliferation, causing knots to form in the smaller blood vessels, such as

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

, restricting the flow of blood. This may be due to BadA's inducing the transcription of proangiogenic factors, as it activates of

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

as well as

hypoxia-inducible factor Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex wa ...

1. The head domain of BadA is more complex than other TAAs. It is thought to be a

chimera Chimera, Chimaera, or Chimaira (Greek for " she-goat") originally referred to: * Chimera (mythology), a fire-breathing monster of Ancient Lycia said to combine parts from multiple animals * Mount Chimaera, a fire-spewing region of Lycia or Cilicia ...

or, in other words, a combination of YadA and Hia head domains. This combination gives insight into how the pathogenicity of Gram-negative bacteria has

evolved Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation t ...

over time. BadA also contains a neck domain, an extended coil-coil stalk, and beta-barrel C terminal membrane anchor.

Clinical effects

Infection process

The process of infection is complicated. The invasive bacterium must overcome many barriers in order to infect its host, including environmental barriers, physical barriers and

barriers. The bacterium must enter the host's body and, in the case of ''Yersinia sp.'', invade the host

intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

. Then the Trimeric Autotransporter Adhesin must adhere to the layer of cells found on the internal surface, the

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

, in the intestine by using its head to bind to proteins found in the

such as

, and

. It is important that these outer-membrane adhesins make physical contact with the receptors found on the host cell. This means that the adhesin must be long enough to extend beyond the

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

layer in the outer membrane of the bacterium and interact with the

glycan The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate p ...

layer of the host cell. Once it has done so, it may bind to the ECM of the host cell. TAAs are a type of microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). In other words, they are a complex that aids adhesion to the ECM.

Type V secretion system (T5SS)

Secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...

is one method of transferring substances across the

. Gram-negative bacteria have very different cell wall structures in comparison to Gram-positive bacteria. Gram-negative bacteria have three layers: The innermost layer is named the inner membrane; the middle layer, named the

periplasmic space The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found that ...

, is a space containing a thin layer of

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ...

; and the third layer is named the outer membrane, which contains

lipopolysaccharides Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer me ...

. In Gram-negative bacteria, the secretary pathway is very different from that of

eukaryotes Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...

bacteria, mainly due to the difference in cell wall structure. Trimeric Autotransporter Adhesins use a particular secretion pathway, named type V secretion system (T5SS). Gram-negative bacteria must secrete

, since they have an outer membrane that makes it hard for them to stick to and infect the host. The outer membrane is useful, as it allows the bacteria to colonize, and adds another layer of protection. However, the outer membrane is a barrier for the secretion of proteins, and it requires energy to transport proteins across the outer membrane. Hence, the T5SS pathway overcomes this problem. T5SS uses Sec-machinery system to work. The

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

Sec translocase is found to be present on the inner membrane. Such Sec-dependent systems do not need to use energy, unlike Sec-independent machinery, which uses other forms of energy such as

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...

(ATP) or a

proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...

gradient In vector calculus, the gradient of a scalar-valued differentiable function of several variables is the vector field (or vector-valued function) \nabla f whose value at a point p is the "direction and rate of fastest increase". If the gradi ...

. Since it can transport things across the outer membrane without the need to generate a new form of energy, it earned the name ''autotransporter'', since it transports proteins ''autonomously'', in other words, by itself. The Sec-dependent system is divided into three pathways. TAAs are one of those pathways and also go by the name ''type Vc secretion pathway''. The mechanism is split into two. First, the protein must move across the inner membrane or, in other words, translocate, in a Sec-dependent manner via the

. The signal peptide on the N-terminus acts as a temporary tether to hold it in place. Next, it must move to the outer membrane. The trimerisation aids translocation, and no translocation would occur without its beta-barrel membrane anchor. The type V secretion system is described as non-fimbrious, meaning that the bacterial cells do not use long physical appendages named

pili Pili may refer to: Common names of plants * ''Canarium ovatum'', a Philippine tree that is a source of the pili nut * ''Heteropogon contortus'', a Hawaiian grass used to thatch structures Places * Pili, Camarines Sur, is a municipality in the ...

to attach to one another.

Evading the host's immune system

The TAAs can help prevent the bacteria from being destroyed by the host's immune system. In particular in the case of certain ''Yersinia spp.'', the TAA YadA has a role in

, serum resistance,

complement inactivation A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...

, and

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

resistance. All of these methods prevent the bacteria from being eliminated by the host and ensure its survival.

References

External links

The TAA database, based at the Max Planck Institute
Protein families Protein domains Virulence factors Gram-negative bacteria Secretion Membrane proteins {{portal bar, Biology

Molecular structure

Extended Signal Peptide Region domain

N-terminal head domain

YadA-like head

Trp ring

GIN

Neck domain

ISneck domain

Stalk domain

C-terminal membrane anchor domain

Model proteins

YadA protein

NadA protein

UspA1 protein

Hia protein

BadA protein

Clinical effects

Infection process

Type V secretion system (T5SS)

Evading the host's immune system

See also

References

External links