molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

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

Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. 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 * Host Island, in the Wilhelm Archipelago, Antarctica People * ...

cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...

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_junction, cell junc ...

. 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, monomer, monomers.Quote: ''Oligomer molecule: A molecule of intermediate ...

coiled-coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a v ...

adhesins Bacterial 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 ...

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

virulence factors Virulence factors (preferably known as pathogenicity factors or effectors in botany) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following: * co ...

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

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

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

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

, 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, intense headache, vomiting and neck stiffness and occasion ...

. Most bacteria infect their host through a method named the

secretion 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 mec ...

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 (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

, for example,

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

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 col ...

, 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 electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...

, 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 amin ...

head domain, a stalk domain, and a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy 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 t ...

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 chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

), N2, H2 and C (

cleavage Cleavage may refer to: Science * Cleavage (crystal), the way in which a crystal or mineral tends to split * Cleavage (embryo), the division of cells in an early embryo * Cleavage (geology), foliation of rock perpendicular to stress, a result of ...

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 manage ...

. 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 guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

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 (more accurately "diderm") bacteria. Using cryo-electron micros ...

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 constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...

. 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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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 aromat ...

. 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. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

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 depro ...

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 gene ...

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 An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...

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 Complement may refer to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class collections into complementary sets * Complementary color, in the visu ...

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 structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...

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 (β barrel) is a beta sheet (β 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 ...

. 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. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

chain through the

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

, 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. Gram-negative bacteria form two lipid bilayers in their cell envelopes - an inner membrane (IM) that encapsulates the cytoplasm, and an outer membrane (OM) that encapsulates the p ...

. 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: * , Japanese actress * , Japanese footballer *, Japanese high jumper * , Japanese voice actor *Lena Yada (born 1978), Japanese-American model, actress ...

of ''

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

'' * NadA of ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as the 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 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 in ...

'' * Hia and Hsf of ''

Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, Motility, non-motile, Coccobacillus, coccobacillary, facultative anaerobic organism, facultatively anaerobic, Capnophile, capnophili ...

'' * BadA of ''

Bartonella henselae ''Bartonella henselae'', formerly ''Rochalimæa henselae'', is a bacterium that is the causative agent of cat-scratch disease ( bartonellosis). It primarily infects red blood cells and endothelial cells and is transmitted to humans through scratch ...

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 '' ...

'' ''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 (malleus, incus, and stapes), which transfer the vibrations ...

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 ciliated pseudostratified columnar epithelium a type of columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways ...

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 gene ...

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) 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 may feel tired ...

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

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

, such as those undergoing

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

or fighting

AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

, 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 ...

. This a condition where

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

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 Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...

undergo uncontrolled

proliferation Proliferation may refer to: Weapons *Nuclear proliferation, the spread of nuclear weapons, material, and technology *Chemical weapon proliferation, the spread of chemical weapons, material, and technology *Missile proliferation, the spread of lon ...

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

capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...

, 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 family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

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 also respond to instances of pseudohypoxia, such as thiamine deficiency. Both hypoxia an ...

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 the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...

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 tract is the largest of the body's systems, after the cardiovascular system. T ...

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 ...

. 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 a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

, 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 Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

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 ...

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 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 mec ...

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 (more accurately "diderm") bacteria. Using cryo-electron microsco ...

, 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 layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

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

lipopolysaccharides Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

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

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

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. The Gram stain is ...

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 An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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 a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

(ATP) or a

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

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

. 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 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 Serum may refer to: Biology and pharmacology *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity *Serous fluid, any clear bodily fluid Places *Serum, Ind ...

resistance,

complement inactivation Complement may refer to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class collections into complementary sets * Complementary color, in the visu ...

, and

phagocytosis Phagocytosis () is the process by which a cell (biology), 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 ph ...

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