Type III secretion system

from Wikipedia, the free encyclopedia
Parent
Cell  (gram-negative bacterial)
Gene Ontology
QuickGO

The type III secretion system (engl Type III secretion system;. As TTSS or T3SS hereinafter) is a protein structure (sometimes referred to as organelle considered), which in some negative Gram bacteria occurs.

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

overview

The term “type III secretion system” was first used in 1993 . This secretion system differs from at least five other bacterial secretion systems . The T3SS occurs only in Gram-negative, mostly pathogenic , bacteria. It is estimated that 25 types of bacteria own the system. The best-researched T3SS are known from the species Shigella (causes bacterial dysentery ), Salmonella ( typhus ), Escherichia coli ( enteritis , colitis ), Burkholderia ( snot ), Yersinia ( plague ) and Pseudomonas (infects humans , animals and plants ).

The T3SS consists of around 30 different proteins, the T3S proteins, in each type of bacteria. This makes it one of the most complex secretion systems. Its structure is very similar to that of flagella . These are long, extracellular organelles that are used to move the bacteria. Some proteins involved in T3SS have amino acid sequences similar to those of flagella proteins . Some of the bacteria that possess T3SS also have flagella and are motile ( Salmonella , for example). Others have no flagella and are immobile ( Shigella , for example). Indeed, type III secretion is used for the exposure of both infectious proteins and flagellar proteins. The term "type III secretion" is mainly used to denote 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 infect millions of people and kill hundreds of thousands each year, mostly in developing countries . Traditional antibiotics have been effective against these bacteria in the past, but resistant strains keep popping up. The elucidation of the mechanism of the T3SS and the development of specific drugs have become an important goal of many research groups worldwide since the late 1990s.

T3S proteins

T3S proteins can be classified into three groups:

  • Structural proteins: make up the base, inner rod and needle.
  • Effectors: are secreted in host cells and support the infection .
  • Chaperones : bind effectors in the bacterial cytoplasm, protect them from breakdown and aggregation, ie "stick together" and guide them towards the needle complex.

Most T3S proteins belong to operons . Such operons are found in some species on the bacterial chromosome , in others on their own plasmid . For example, Salmonella has a region on the chromosome, the so-called Salmonella Pathogenicity Island ( SPI ), in which almost all T3S genes can be found. Shigella, on the other hand, has a large virulence plasmid on which all T3S genes are located.

Effector proteins to be secreted must be recognized by the system because they are located in the cytoplasm along with thousands of other proteins. Almost all effectors carry a secretion signal - a short amino acid sequence, usually at the beginning (N-terminus) of the protein, that the needle complex can recognize.

Induction of secretion and gene induction

Little is known about the mechanism by which secretion is triggered (= induction). Contact of the needle with a host cell induces secretion. In Yersinia and Pseudomonas , the secretion can also be independent of a host cell by decreasing the calcium ion - concentration in the culture medium to induce (which is prepared by adding chelators such as EDTA or EGTA reached) in Shigella by the aromatic dye Congo Red . With these and other methods, type III secretion is artificially induced in research laboratories.

Bacterial secretion behavior can also be induced in infected organisms by signals other than host cell contact, such as temperature , pH , osmolarity and oxygen concentration . In Shigella this occurs through cholesterol , a lipid found in almost all eukaryotic cell membranes , in Salmonella through the ions formate and acetate . These ions are found in the ileum , a typical site of Salmonella infection . Conversely, in Salmonella the ions butyrate and propionate stop secretion; these ions are found in the appendix .

The above signals regulate secretion either directly or through gene regulation . Some T3S transcription factors are known, including T3S chaperones (see above). Chaperones could bring about a positive regulation of the gene that codes for an effector: as long as there is no secretion, the chaperone is bound to the effector in the cytoplasm. When secreted, the effector and chaperone separate. The former is secreted; the latter acts as a transcription factor by binding to the coding gene, inducing its transcription and thereby causing the production of further effector molecules.

T3SS-mediated infection

How effectors of the T3SS penetrate a host cell is not yet fully understood. They first get into the base of the needle complex and then move through the needle towards the host cell. According to previous ideas, the needle itself should drill holes in the membrane of the host cell, but this has been refuted. It is now known that certain effectors called translocators are excreted first and create an opening or channel (a translocon ) in the host cell's membrane. The remaining effectors can penetrate the host cell through the translocon. Mutated bacteria that lack the translocators can excrete the remaining effectors; However, these do not penetrate the host cell, so that damage to the same (and thus the pathogenic effect ) does not occur. As a rule, each T3SS has three translocators. Some translocators have a double role in that they also act as effectors inside the host cell after the translocon has been generated.

Many types of bacteria depend on entering a host cell in order to multiply and spread within a tissue. Such bacteria spend effectors in a host cell, which causes the host cell to enclose the bacterium and take it into its interior (= phagocytosed ). To do this, the effectors reverse the polymerization of actin filaments in the host cell's cytoskeleton .

It has been proven that T3SS effectors can also intervene in the cell cycle of host cells and trigger programmed cell death (= apoptosis ). One of the most studied effectors is IpaB from Shigella flexneri . IpaB has the above-mentioned dual role as a translocator and an effective effector inside cells, and it inflicts a variety of damage on host cells. In 1994 it was shown that IpaB triggers apoptosis in macrophages after phagocytosis of the bacterium by means of the enzyme caspase 1 .

Certain effectors of the T3SS ( activator-like effectors , TAL effectors ) have a positive gene-regulating effect . Such TAL effectors of the bacterium Xanthomonas have been well studied . When these get into plants, they can penetrate the nucleus of a plant cell, bind to promoters and cause the transcription of plant genes that promote infection by the bacterium. To do this, they specifically bind to tandem repeats of the host cell DNA.

Unsolved 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 only injected into the target cells in tiny amounts. The amount or concentration of the vast majority of effectors thus remains unknown. Without known amounts, however, the physiological effects are often difficult to assess, although the biochemical function of many effectors is known. Nevertheless, the molecular function of many effectors remains unclear. The location of each protein is also not fully understood.
  • Length of the needle . It is not known how the bacterium “knows” when a new needle is an appropriate length. Several theories exist, including the existence of a "yardstick protein" connecting the tip of the needle to the base. As new needle subassemblies are added to the tip, the ruler protein stretches, “reporting” the length of the needle to the base.
  • Energetics . The force with which the proteins are driven out through the needle is not fully known. An ATPase is bound to the base of the needle complex and takes part in guiding proteins towards the needle. It is unclear whether it provides the energy for transport.
  • Secretion signal . As mentioned above, effector proteins have a secretion signal that helps the secretion system to distinguish these effectors from other proteins. The prerequisites and the exact detection mechanism are currently unknown.
  • Activation of secretion . The bacterium must recognize the right time to secrete. Unnecessary secretion when there is no host cell nearby is uneconomical for the bacterium in terms of energy and building blocks. The bacterium can sense contact between the needle and a host cell, but the mechanism is unknown. Some theories assume subtle conformational changes in the needle structure upon contact, which then cause changes in the conformation of the base and thus switch on secretion.
  • Tying 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.

See also

swell

  1. ↑ TCDB : 3.A.6
  2. ↑ A. Blocker, N. Jouihri et al. a .: Structure and composition of the Shigella flexneri "needle complex", a part of its type III secreton. In: Molecular microbiology. Volume 39, Number 3, February 2001, pp. 652-663, ISSN  0950-382X , PMID 11169106 .
  3. ^ Salmond GP, Reeves PJ: Membrane traffic wardens and protein secretion in Gram-negative bacteria . In: Trends Biochem Sci . 18, 1993, pp. 7-12.
  4. ↑ A: Zychlinsky, B. Kenny, R. Menard, MC Prevost, IB Holland, PJ Sansonetti: IpaB mediates macrophage apoptosis induced by Shigella flexneri. In: Mol Microbiol 11 (4): 1994. pp. 619-627, doi: 10.1111 / j.1365-2958.1994.tb00341.x , PMID 8196540 .
  5. ↑ H. Hilbi, JE Moss, D. Hersh, Y. Chen, J. Arondel, S. Banerjee, RA Flavell, J. Yuan, PJ Sansonetti, A. Zychlinsky: Shigella-induced Apoptosis Is Dependent on Caspase-1 Which Binds to IpaB. In: J Biol Chem 273 (49) 1998, pp. 32895-32900, doi: 10.1074 / jbc.273.49.32895 , PMID 9830039 .
  6. ↑ Boch, J .; Bonas, U. (2010). XanthomonasAvrBs3 Family-Type III Effectors: Discovery and Function. In: Annual Review of Phytopathology. 48. pp. 419-436, doi: 10.1146 / annurev-phyto-080508-081936 , PMID 19400638 .
  7. ↑ Moscou, MJ; Bogdanove, AJ (2009). A Simple Cipher Governs DNA Recognition by TAL Effectors. In: Science. 326 (5959): 1501. bibcode : 2009Sci ... 326.1501M , doi: 10.1126 / science.1178817 , PMID 19933106 .