Molecule of the Moment: Acylhomoserine lactone

Source: Many species of Gram-negative bacteria use acylated homoserine lactones (AHLs) to regulate and control a number of different phenomena, including the production of light and the expression of virulence factors. 

Chemical Structure: The basic structure of AHLs features a lactone (here, a five membered ring in which an ester is contained within the ring) connected through an amide bond (or N-acyl linkage) to a flexible carbon chain, usually featuring a ketone group. Twelve different analogues of this basic structure have been found in Nature. These differ in the length of the acyl chain and all share the lactone ring.

this is an acylhomoserine lactone.

this is an acylhomoserine lactone.

Historical background:  According to a 2001 review by Greenberg et al., when AHLs were first discovered in the 1960s, "biologists weren't ready for the idea that bacteria were talking to each other. Nevertheless, that is exactly what they do."

Since these seminal discoveries,the biosynthesis and use of AHLs to mediate signaling has been discovered in various species of bacteria that inhabit diverse niches. AHL signaling is associated with a process known as quorum sensing. Quorum sensing is the process through which organisms respond to signals in a cell-density dependent manner. Quorum sensing is mediated through a variety of signal molecules, including AHLs with various acyl chain lengths, as well as two other chemically distinct molecules called furanosylborate and  cyclic thiolactone. Quorum sensing is a common signaling strategy when coordinated gene expression is needed by a community of bacteria. For instance, quorum sensing using AHLs is used by bacteria, such as Vibrio cholera, to switch on virulence genes under certain conditions that favor a pathogenic lifestyle.

In the case of AHLs, bacteria biosynthesize a species-specific AHL at a basal level. As the local population of bacteria increases, AHL accumulates in the surrounding medium. At a certain cell density (and corresponding concentration of AHL), there is enough AHL in the cell cytoplasm that a complex forms between AHL and a protein called LuxR. When the AHL-LuxR complex is formed, this complex acts as a promoter of gene expression at certain genetic loci. In all bacteria that use AHLs to do quorum sensing, one of the loci that gets upregulated by LuxR-AHL complex is the gene that is responsible for the biosynthesis of AHL.  In this way, as the local concentration of bacteria increases, AHL production increases in an exponential manner. Other genetic loci that are regulated by LuxR include those involved in turning on light production in the symbionts of the bobtail squid (see below) and virulence factors (such as the production of proteins that allow bacteria to invade human cells) in the case of pathogenic bacteria.

Uses (just a few of many):  At Chemical Intuition, our favorite use of AHL is by the bacteria that live in the light organ of the bobtail squid. These symbionts include the species Vibrio fischeri and Vibrio harveyi. In these bacteria, AHL biosynthesis and the protein LuxR (mentioned above) are encoded in a set of genes clustered together on the bacterial chromosome. These genes are called the lux genes for the enzyme called luciferase, which is also encoded in this cluster of genes. The luciferase protein performs a reaction that results in the production of light, making these bacteria bioluminescent organisms!  By coordinating gene expression through AHL-mediated quorum sensing, the bacteria can quickly turn on light production when cell density is high.

Dangers: In contrast to our last molecule of the moment, atropine, one could likely consume a reasonable quantity of purified AHLs and survive to tell the tale.

Fact that can be used to impress friends/foes at a cocktail party:  You can impress your friends by telling them the strange details of the Bobtail squid's camouflage strategy. The squid does a maneuver known as "counter illumination," a strategy in which the squid tries to match the intensity of light coming from the moon to reduce its silhouette in the water.  The squid produces light so that it doesn't cast a shadow at night under moonlight, which helps the squid evade predators. The bacterial symbionts are key to the squid's camouflage strategy. The squid's symbiotic bacteria live in the squid's so called "light organ." This bacterial-filled light organ is tricked out with accessories that give the squid fine-tuned control of its light production. These accessories include special tissues that reflect or focus light and an ink sac that allows the squid to dial in the intensity of the light its light organ emits.