6.2: Bacterial Signaling
At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that results in a shift in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell membrane into the extracellular space. AIs can move passively along a concentration gradient out of the cell, or be actively transported across the bacterial membrane.
The Extracellular Concentration of AIs Gives Signals to Bacteria
When cell density in the bacterial populations is low, the AIs diffuse away from the bacteria, keeping the environmental concentration of AIs low. As bacteria reproduce and continue to excrete AIs, the concentration of AIs increases, eventually reaching a threshold concentration. This threshold permits AIs to bind membrane receptors on the bacteria, triggering changes in gene expression across the whole bacterial community.
Many bacteria are broadly classified as gram positive or gram negative. These terms refer to the color that the bacteria take on when treated with a series of staining solutions which were developed by Hans Christian Joachim Gram over a century ago. If bacteria pick up a purple color, they are gram-positive; if they look red, they are gram-negative. These stain colors are picked up by the bacteria because of the different chemistries of their cell walls. The different composition of the bacterial cell walls determine the ways the bacteria interact with each other and their environment and are often directly involved in causing disease. For example, the cell walls of gram-negative bacteria are mainly made of lipopolysaccharide, also known as endotoxin, which causes septic shock in a patient’s blood.
Quorum Sensing in Gram Positive and Gram Negative Bacteria
In gram-positive bacteria, quorum sensing most often occurs in two steps. First, the AI, an autoinducing peptide (AIP), binds a membrane receptor when the external concentration is sufficiently high. The binding activates internal enzymes, so-called second messenger kinases that phosphorylate transcription factors. The transcription factors then regulate the expression of different genes.
In the case of many gram-negative bacteria, however, quorum sensing takes place in a one-step process. When the external concentration of AIs reaches the threshold, the AI crosses the membrane (via a transporter) and reenters the cell. Once inside, it may directly interact with transcription factors to regulate gene expression. This type of signaling does not require an intermediary or second messenger. The AI itself is the messenger. However, even without a second messenger, the intracellular signaling can be complicated.
Signaling in a Bacteria That Produces Light
One example of this is the bacteria Photorhabdus luminescens, which is gram negative. It produces autoinducer 2 (AI-2) as a quorum sensing signal and as an intracellular signal. The bacteria release AI-2 into the environment. When AI-2 reaches threshold levels outside the bacterial cells, AI-2 binds to an ATP-binding cassette (ABC) transporter on the bacterial membrane, and it is re-internalized by the ABC transporter. Then, an intracellular kinase, LsrK, phosphorylates AI-2 itself. Once activated in this way, AI-2 itself can perform as a transcription factor, activating genes which encode the enzyme luciferase. Luciferase produces light when catalyzing specific reactions. Thus only when the Photorhabdus luminescens population reaches a critical density can you see their bioluminescence. It has been suggested that this bacteria was responsible for the bluish-green glow seen in the wounds of some US Civil War soldiers after the battle of Shiloh.
Quorum Signaling and Bacterial Infections of Implanted Medical Devices
The spread of bacteria across the surface of medical implants occurs through quorum signaling and can cause life-threatening infections. A great deal of research is ongoing, to find ways to stop bacterial biofilms from forming in medical settings. Much of this research focuses on developing new materials that are not amenable to bacterial growth. However, biological compounds, including substances produced by some kinds of bacteria, are also being investigated for their bacterial inhibition properties.