A Type VIII secretion system is a type of

secretion system 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 classi ...

found within the inner and outer membranes of

gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

. This system is also referred to as the curli biogenesis pathway or the extracellular nucleation-precipitation pathway. It is associated with the formation of

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

s and infecting hosts.

Curli The Curli protein is a type of amyloid fiber produced by certain strains of enterobacteria. They are extracellular fibers located on bacteria such as ''E. coli'' and ''Salmonella'' spp. These fibers serve to promote cell community behavior throu ...

formation is especially efficient at evading the host's immune system due to the subunits being able to quickly assemble in a single process and not having intermediates. This system is associated with curli-specific genes and utilizes multiple proteins in its process to form curli fibers. These proteins include CsgA CsgB, CsgC, CsgD, CsgE, CsgF, and CsgG. Type VIII secretion system facilitates the assembly and translocation of curli fibers.

Curli fibers and their virulence

Curli fibers are made through the curli biogenesis system, also known as the type VIII secretion system, and are essentially long, linear structures made from proteins that are secreted to the outside of the cell into its surrounding environment. They are made mostly by gram-negative bacteria and, upon secretion, they form compact clusters around the outside of the cell. The main function of the curli fibers involves their interactions with biofilms. In pathogenic bacteria, curlis can contribute to virulence by helping in cell invasion and activating the innate immune response. Knowing how curli fibers are made, and how the type VIII secretion system works, can help develop an inhibitor to stop or reduce the production of these curli fibers and overall reduce the virulence of the bacteria that produce them. Understanding these mechanisms can also play a big role in creating treatments for infections that are associated with biofilms.

Curli development and control

Curli biogenesis is an adaptable process that uses a direct route and can transform from an intrinsically disordered complex system to a simple

amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the hu ...

state. The proteins in this system are encoded by two separate

operons In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

. One operon codes for CsgA, CsgB, and CsgC, whereas the other codes for CsgD, CsgE, CsgF, and CsgG. The two major subunits involved in this process are CsgA and CsgB, with CsgA being the most important to the system. CsgA and CsgB are responsible for the system's control and extension of fibers. CsgA can transition from a disorder to an ordered amyloid state while the CsgB functions as a nucleator to help promote the polymerization of CsgA. Then, CsgC is introduced as a chaperone and works to keep CsgA from reaching the amyloid state prematurely. The process by which CsgC prevents this is still misunderstood, but the positive charge beta-strand is most theorized. CsgG is part of a secretion channel that facilitates the translocation of CsgA to 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 tha ...

. CsgE functions as a specificity binder to help guide CsgA to the CsgG secretion channel so that CsgA will be the correct conformation for

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

. Throughout this process, CsgF interacts with CsgA and CsgB to help enhance the assembly of CsgA and coordinate the nucleating activity of CsgB. CsgD functions as a

transcriptional regulator In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...

that influences the expression of CsgA and CsgB through environmental factors. The resulting structure is made up of alternating CsgA and CsgB subunits with CsgF unit at the base and the entirety of the structure will be on the outside of the bacterial cell.

Secretion mechanisms

The secretion of the assembled units requires energy. Energy within a bacterial cell is typically supplied by

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or GTP, proton motive force, or other

membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charge ...

s. However, with type VIII secretions systems, it is unlikely that energy is derived from one of these typical methods due to its location on the outer membrane of gram-negative bacteria. The CsgG protein complex is the channel used to allow the assembled CsgA, CsgB, and CsgF subunits to move through the membrane to the outside of the cell where they remain in close proximity to the CsgG protein. It is thought that the energy released from the subunits folding and unfolding as well as the potential from the movement of the subunits across the membrane gives the necessary energy for secretion. While the type VIII secretion pathway is most desirable, some bacterial species may use th
functional amyloid pathway
or Fap, to form a biofilm so it can attach to surfaces.

References

{{reflist Secretion Cell biology