Type three secretion system

The type III secretion system (English Type III secretion system, TTSS or T3SS as abbreviated ) is a protein structure ( sometimes regarded as organelle ) that occurs in some Gram- negative bacteria.

This structure is used for the secretion of bacterial proteins in eukaryotic cells. These proteins enable the bacteria, the eukaryotic cells ( hosts ) to infect. The proteins are transferred directly from the bacterial cell into the host cell by means of a needle structure, the characteristics of the T3SS.

Overview

The term " type III secretion system " was used first time in 1993. This secretion system differs from at least five other bacterial secretion systems. The T3SS occurs only in Gram-negative, mostly pathogenic bacteria. An estimated 25 species of bacteria possess the system. The most researched T3SS are from species of Shigella ( causes dysentery ), Salmonella ( typhoid ), Escherichia coli ( enteritis, colitis), Burkholderia ( glanders ), Yersinia ( plague ) and Pseudomonas ( infects humans, animals and plants ) are known.

The T3SS consists in each bacterial species from about 30 different proteins. This makes it one of the most complex secretion systems. Its structure is that of flagella very similar. These are long, extracellular organelles that serve the movement of the bacterium. Some proteins that are involved in the T3SS, have similar amino acid sequences as Flagellenproteine ​​. Part of the T3SS owning bacteria also has flagella and is movable (Salmonella, for example ). Others have no flagella and are immobile ( Shigella, for example ). In fact, the type III secretion for both suspension of infectious proteins and Flagellenproteine ​​used. The term " type III secretion " but is primarily used to refer to the infection apparatus. It is debated whether T3SS and flagella are evolutionarily related.

The T3SS is necessary for the pathogenicity of the bacterium. Defects in the T3SS often mean the loss of infectivity. Diseases that cause the above T3SS bacteria that infect millions of people and kill hundreds of thousands every year, mainly in developing countries. Traditional antibiotics in the past were efficient against these bacteria, but resistant strains emerge again and again. The elucidation of the mechanism of T3SS and the development of specific drugs have become the world from the late 1990s, an important goal of many research groups.

Structure

The hallmark of the T3SS is the needle ( needle complex known as general; Injectisom is also called ). To secreting proteins are transferred through the needle from the bacterial cytoplasm to the cytoplasm of the host cell directly. The two cytoplasmic organelles are separated by three membranes: the double membrane of the Gram- negative bacterium and the eukaryotic membrane. The needle allows smooth passage through this highly selective and almost impermeable membranes. A single bacterium usually has several hundreds of needle complexes that are distributed in its membrane.

The needle complex begins in the cytoplasm of the bacteria passes through the two membranes, and protrudes out of the cell. The membrane-bound part is the base of the T3SS. The extracellular part is the needle. A so-called inner bar ( engl. inner rod ) connects needle and base. The needle itself, although the largest and most impressive part of the complex consists of several subunits of a single protein. Therefore, the majority of the various proteins T3S consists of these, which form the base and are secreted. As mentioned above, the needle complex is very similar to the bacterial flagellum. More specifically, the needle base of Flagellenbasis is very similar. The needle itself is the Flagellenhaken analog, a structure that connects the Flagellenfilament with the base.

The base is composed of several circular rings, and the first structure, which is built in the manufacture of a new needle. When the base is ready, it serves as Sekretionsmaschine for the outer proteins ( ie the needle ). When the whole complex is finished, is a so-called Spezifizitätswechsel was: The system ceases to secrete proteins and needle begins (if required) to secrete proteins to enter host cells. It is believed that the needle is constructed from bottom to top. Needle subunits accumulate on one another, so that the subunit at the tip is added as a last resort. The needle subunit is one of the smallest T3SS proteins, with a weight of 9 kDa. Each needle is from approximately 100 to 150 subunits.

The T3SS needle is about 60-80 nm long and ( from the outside) 8 nm wide. A certain minimum length is necessary so that other extracellular structures of the bacterium (such as adhesin and lipopolysaccharides ) not interfere with the secretion. The hollow tube inside the needle is only 3 nm wide, which means that the secreted proteins must be unfolded, when they pass through the needle. Folded most effectors would be too large for the needle.

T3S proteins

T3S proteins can be classified into three groups:

• Structural proteins forming the base, the inner rod and the needle.
• Effectors: are secreted into host cells and support the infection.
• Chaperone: bind to effectors in the bacterial cytoplasm, protect them from degradation and aggregation, ie " sticking together " and pass it towards the needle complex.

Most T3SS proteins belong to operons. These operons are located in some species on the bacterial chromosome and the other on a separate plasmid. Salmonella, for example, has a region on the chromosome, known Salmonella pathogenicity island (SPI), in which almost all T3SS genes are found. Shigella, however, has a large virulence plasmid, on which all the T3SS genes.

To secreting effector proteins must be recognized by the system, because they are located in the cytoplasm along with thousands of other proteins. Almost all Effektore carry a secretion signal, a short amino acid sequence, typically at the start ( N-terminus ) of the protein, which can recognize the complex needle.

Induction of secretion

Contact of the needle with a host cell triggers secretion. Not much is known about the trigger mechanism ( see below). Not only host cells can induce the secretion. The secretion can be induced by decreasing the concentration of calcium ions in the nutrient medium ( in Yersinia and Psudomonas, which is by the addition of chelators such as EDTA or EGTA is reached). The aromatic dye Congo Red induces secretion in Shigella. With these and other method type III secretion is induced artificially in research laboratories.

Induction of secretion by external signals out of contact with host cells occurs also in vivo in infected organisms. The bacteria perceive signals such as temperature, pH, osmolarity, and oxygen concentration, and use them to "decide" the best time for secretion to. For example, cholesterol, lipid, which is in almost all eukaryotic cell membranes, induced secretion in Shigella. The ion formate and acetate induce secretion in Salmonella. These ions are found in the ileum, the major site for Salmonella infections.

The above-mentioned signals regulate the secretion either directly or by genetic mechanisms. Some T3S transcription factors are known. Part of the T3S chaperones also serves as transcription factors. This is done by a feedback mechanism. At times in which there is no secretion, chaperone bound to the effectors in the cytoplasm. When secretion chaperones and Effektore to separate tags. The latter are secreted and former then act as transcription factors. They bind to genes coding for their respective Effektore and induce their transcription and thereby production of further Effektore.

T3SS -mediated infection

T3SS effectors penetrate with the needle complex one at the base and pass through the needle in the direction of the host cell. How exactly penetrate the effectors into the host cell, is usually unknown. Earlier been proposed that the needle itself can cause holes in the host membrane; but this was later refuted. It is now known that some effectors, collectively called translocators, are first secreted and a pore or a channel ( a translocon ) in the host membrane produce. Through the pore the remaining Effektore can enter the host cell. Mutated bacteria, in which the translocators missing, although can Effektore secrete but can not deliver into the host cell, these and therefore are not pathogenic. As a rule, each T3SS translocators three. Some translocators have a dual role. After the formation of the pore, they enter the cell, where they serve as a "real " effectors.

Unresolved issues

Hundreds of articles about T3SS have been published since the mid- 1990s. Nevertheless, many questions remain open:

• T3SS proteins and effectors. Most T3SS effectors are injected in tiny amounts into the target cells. The amount or concentration of most effectors thus remains unknown. Without known amounts but are the physiological effects often difficult to estimate, although the biochemical function of many effectors is known. Nevertheless, the molecular function of many effectors remain unclear. The localization of each protein is not fully elucidated.
• Length of the needle. It is unknown how the bacteria " knows" when a new needle has reached a suitable length. There are some theories among others the existence of a " standard protein ", which connects the tip of the needle to the base. If new needle subunits are added at the top, the scale protein and stretches " reports" so that the base, the length of the needle.
• Energetics. What is the force the proteins are driven by the needle to the outside is not fully known. ATPase is bonded to the base of the needle and decreases the conduction of complex proteins in the direction of the needle part. Whether it provides the energy for the transport is unclear.
• Secretion. As mentioned above, effector have a secretion signal helps the secretion system to distinguish between these effectors from other proteins. The conditions and the accurate detection mechanism are currently unknown.
• Activation of secretion. The bacterium must recognize the right time for secretion. Unnecessary secretion when no host cell is in the vicinity is not economical for the bacterium when it comes to energy and building blocks. While the bacterium can sense a contact of the needle with a host cell, the mechanism is unknown. Some theories suggest the fine conformational changes of the needle structure upon contact, which then cause changes in the conformation of the base and thus activate the secretion.
• Binding of chaperones. The time at which chaperones bind to their effectors ( whether during or after translation ), is unknown, as is the way in which chaperones and effectors separate from each other prior to secretion.

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