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 surrounding medium. They are a key component of the phenomenon of quorum sensing: as the density of quorum-sensing bacterial cells increases, so does the concentration of the autoinducer. A bacterium's detection of an autoinducer above some minimum threshold triggers altered gene expression.

Performed by both Gram-negative and Gram-positive bacteria, detection of autoinducers allows them to sense one another and to regulate a wide variety of physiological activities, including symbiosis, virulence, motility, production of antibiotics, and formation of biofilms.

Autoinducers take a number of different forms depending on the species of bacteria, but their effect is in many cases similar. They allow bacteria to communicate both within and between species, and thus to mount coordinated responses to their environments in a manner that is comparable to behavior and signaling in higher organisms. Not surprisingly, it has been suggested that quorum sensing may have been an important evolutionary milestone that ultimately gave rise to multicellular life forms.

The term autoinduction was first coined in 1970, when it was observed that the bioluminescent marine bacterium Vibrio fischeri produced a luminescent enzyme (luciferase) only when cultures had reached a threshold population density. At low cell concentrations, V. fischeri did not express the luciferase gene. However, during the cultures’ exponential growth phase, the luciferase gene was rapidly activated. This phenomenon was called autoinduction because it involved a molecule (the autoinducer) produced by the bacteria themselves that accumulated in the growth medium and induced the synthesis of components of the luminescence system. Subsequent research revealed that the actual autoinducer used by V. fischeri is an acylated homoserine lactone (AHL) signaling molecule.

In the most simplified quorum sensing systems, bacteria only need two components to make use of autoinducers. They need a way to produce a signal and a way to respond to that signal. These cellular processes are often tightly coordinated and involve changes in gene expression. The production of autoinducers generally increases as bacterial cell densities increase. Most signals are produced intracellularly and are subsequently secreted in the extracellular environment. Detection of autoinducers often involves diffusion back into cells and binding to specific receptors. Usually, binding of autoinducers to receptors does not occur until a threshold concentration of autoinducers is achieved. Once this has occurred, bound receptors alter gene expression either directly or indirectly. Some receptors are transcription factors themselves, while others relay signals to downstream transcription factors. In many cases, autoinducers participate in forward feedback loops, whereby a small initial concentration of an autoinducer amplifies the production of that same chemical signal to much higher levels.

Primarily produced by Gram-negative bacteria, acylated homoserine lactones (AHLs) are a class of small neutral lipid molecules composed of a homoserine lactone ring with an acyl chain. AHLs produced by different species of Gram-negative bacteria vary in the length and composition of the acyl side chain, which often contains 4 to 18 carbon atoms. AHLs are synthesized by AHL syntheses. They diffuse in and out of cells by both passive transport and active transport mechanisms. Receptors for AHLs include a number of transcriptional regulators called "R proteins," which function as DNA binding transcription factors or sensor kinases.

Gram-positive bacteria that participate in quorum sensing typically use secreted oligopeptides as autoinducers. Peptide autoinducers usually result from posttranslational modification of a larger precursor molecule. In many Gram-positive bacteria, secretion of peptides requires specialized export mechanisms. For example, some peptide autoinducers are secreted by ATP-binding cassette transporters that couple proteolytic processing and cellular export. Following secretion, peptide autoinducers accumulate in extracellular environments. Once a threshold level of signal is reached, a histidine sensor kinase protein of a two-component regulatory system detects it and a signal is relayed into the cell. As with AHLs, the signal ultimately ends up altering gene expression. Unlike some AHLs, however, most oligopeptides do not act as transcription factors themselves.

The free-living bioluminescent marine bacterium, Vibrio harveyi, uses another signaling molecule in addition to an acylated homoserine lactone. This molecule, termed Autoinducer-2 (or AI-2), is a furanosyl borate diester. AI-2, which is also produced and used by a number of Gram-negative and Gram-positive bacteria, is believed to be an evolutionary link between the two major types of quorum sensing circuits.