Autoinducer-2 (AI-2) is a furanosyl borate diester or tetrahydroxy furan (species dependent) that—as the name suggests—is an

autoinducer In biology, an autoinducer is a signaling molecule that enables detection and response to changes in the population density of bacterial cells. Synthesized when a bacterium reproduces, autoinducers pass outside the bacterium and into the surround ...

, a member of a family of

signaling molecule In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

s used in

quorum sensing In biology, quorum sensing or quorum signaling (QS) is the process of cell-to-cell communication that allows bacteria to detect and respond to cell population density by gene regulation, typically as a means of acclimating to environmental disadv ...

. AI-2 is one of only a few known

biomolecules A biomolecule or biological molecule is loosely defined as a molecule produced by a living organism and essential to one or more typically biological processes. Biomolecules include large macromolecules such as proteins, carbohydrates, lipi ...

incorporating

boron Boron is a chemical element; it has symbol B and atomic number 5. In its crystalline form it is a brittle, dark, lustrous metalloid; in its amorphous form it is a brown powder. As the lightest element of the boron group it has three ...

. First identified in the

marine bacterium Marine prokaryotes are marine bacteria and marine archaea. They are defined by their habitat as prokaryotes that live in Marine habitat, marine environments, that is, in the saline water, saltwater of seas or oceans or the brackish water of ...

Vibrio harveyi ''Vibrio harveyi'' is a Gram-negative, bioluminescent, marine bacterium in the genus ''Vibrio''. ''V. harveyi'' is rod-shaped, motile (via polar flagella), facultatively anaerobic, halophilic, and competent for both fermentative and respiratory ...

'', AI-2 is produced and recognized by many

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 ...

and

Gram-positive bacteria 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 ...

. AI-2 arises by the reaction of

4,5-dihydroxy-2,3-pentanedione 4,5-Dihydroxy-2,3-pentanedione (DPD) is an organic compound that occurs naturally but exists as several related structures. The idealized formula for this species is CH3C(O)C(O)CH(OH)CH2OH, but it is known to exist as several other forms resultin ...

, which is produced enzymatically, with

boric acid Boric acid, more specifically orthoboric acid, is a compound of boron, oxygen, and hydrogen with formula . It may also be called hydrogen orthoborate, trihydroxidoboron or boracic acid. It is usually encountered as colorless crystals or a white ...

and is recognized by the two-component sensor kinase LuxPQ in

Vibrionaceae The Vibrionaceae are a family of Pseudomonadota given their own order, Vibrionales. Inhabitants of fresh or salt water, several species are pathogenic, including the type species ''Vibrio cholerae'', which is the agent responsible for cholera. Mo ...

. AI-2 is actively transported by the Lsr ABC-type transporter into the cell in

Enterobacteriaceae Enterobacteriaceae is a large family (biology), family of Gram-negative bacteria. It includes over 30 genera and more than 100 species. Its classification above the level of Family (taxonomy), family is still a subject of debate, but one class ...

and few other bacterial taxa such as ''

Pasteurella __NOTOC__ ''Pasteurella'' is a genus of Gram-negative, facultatively anaerobic bacteria. ''Pasteurella'' species are non motile and pleomorphic, and often exhibit bipolar staining ("safety pin" appearance). Most species are catalase- and oxidas ...

'', ''

Photorhabdus ''Photorhabdus'' is a genus of bioluminescent, gram-negative bacilli which lives symbiotically within entomopathogenic nematodes, hence the name ''photo'' (which means light producing) and ''rhabdus'' (rod shape). ''Photorhabdus'' is known to be ...

'', ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

'', and ''

Bacillus ''Bacillus'', from Latin "bacillus", meaning "little staff, wand", is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-sh ...

'', where it is phosphorylated by LsrK. Then, Phospho-AI-2 binds the transcriptional repressor protein, LsrR, which subsequently is released from the promoter/operator region of the lsr operon – and transcription of the ''lsr'' genes is initiated. AI-2 signalling is also regulated by glucose and cAMP/CRP via the ''lsr'' operon. In the presence of glucose, low levels of cAMP/CRP result in almost no ''lsr'' operon (''lsrABCDFG'') expression. Without glucose, cAMP-CRP is needed to stimulate the ''lsr'' expression, while LsrR represses its expression in the absence of the inducer, phospho-AI-2. As AI-2 accumulates, more AI-2 is taken in via LsrABCD, phosphorylated via LsrK, and the ''lsr'' transcription is de-repressed, enabling even more AI-2 uptake. Doubts have been expressed regarding AI-2's status as a universal signal. Although the ''luxS'' gene, which encodes the protein responsible for AI-2 production is widespread, the latter has mainly a primary metabolic role in the recycling of ''S''-adenosyl-L-methionine, with AI-2 being a by-product of that process. An unequivocally AI-2 related behavior was found to be restricted primarily to organisms bearing known AI-2 receptor genes. Thus, while it is certainly true that some bacteria respond to AI-2, it is doubtful that it is always being produced for purposes of signaling.

Mimicry by host cells

It has been found that in response to bacteria or to disruption of the

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...

mammalian A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

epithelial 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 ...

cells synthesize an AI-2 mimic that triggers quorum sensing and may play an important role in enlisting gut microbes that are known to assist in epithelial healing. In reporting these findings, the researchers write that their results “suggest that crosskingdom communication occurs between

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

cells and bacteria via the AI-2 bacterial quorum-sensing system.”

References

{{Reflist Signal transduction Cell biology Cell communication Cell signaling Tetrahydroxyborate esters Boron heterocycles Furans Heterocyclic compounds with 2 rings