A leukocidin is a type of

cytotoxin Cytotoxicity is the quality of being toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium ...

created by some types of

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 ...

(''Staphylococcus''). It is a type of

pore-forming toxin Pore-forming proteins (PFTs, also known as pore-forming toxins) are usually produced by bacteria, and include a number of protein exotoxins but may also be produced by other organisms such as apple snails that produce perivitellin-2 or earthw ...

. Leukocidins fall into the category of bacterial

invasin Invasins are a class of bacterial proteins associated with the penetration of pathogens into host cells. Invasins play a role in promoting entry during the initial stage of infection. In 2007, Als3 was identified as a fungal invasion allowing ' ...

. Invasins are enzymatic secretions that help bacteria invade the host tissue to which they are attached. Although similar to

exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, sim ...

s, invasins are different in two respects: they work through much less specific mechanisms than exotoxins, and their actions are generally more localized. Leukocidins get their names by killing ("-cide")

leukocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

. Leukocidins target

phagocyte Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...

natural killer cell Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells ...

dendritic cell A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

s, and

T lymphocyte T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s, and therefore affect both innate and adaptive immune responses.

Mechanism of action

Leukocidins are pore-forming toxins, and their model for pore formation is step-wise. First, the cytotoxin's "S" subunit recognizes specific protein-containing receptors, typically G-protein coupled receptors, or an

integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...

on the host cell's surface. The S subunit then recruits a second, "F" subunit. The two subunits dimerize on the host cell surface. This dimerization is followed by oligomerization involving three additional leukocidin dimers, resulting in an octameric prepore complex. The prepore undergoes a structural transition in which its prestem domain extends into the

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes form a continuous barrier around all cell (biology), cells. The cell membranes of almost all organisms and many viruses a ...

, forming a

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 ...

that pierces the target cell membrane, thereby disrupting the structure of the cell and leading to lysis.

Subunits: S and F

The F subunit stands for the "fast" subunit while the S subunit stands for the "slow" subunit. The S subunit is the first to bind the lipid bilayer, recognizing the cell surface receptor. Once bound, the F subunit dimerizes with the S subunit to initiate pore assembly.

Variatiants

There are exceptions to the typical binding pattern of leukocidins. For example: * LukPQ: In this case, the F subunit (rather than the S subunit) recognizes the cell surface receptor. * LukAB: This leukocidin binds to the

CD11b, not a G-protein coupled receptor.

Examples

One notable type of leukocidin is the Panton-Valentine leukocidin.

References

External links

* Bacterial toxins {{biochem-stub