E pluribus unum: out of many, one

Dr. Bonnie Bassler of Princeton University believes that bacterial communication holds the key to new and more effective antibacterial therapies. These therapies could help cure some of the most debilitating diseases around the globe. In February of 2009, Dr. Bassler outlined her strategy in a very accessible TED talk (http://www.ted.com/speakers/bonnie_bassler.html).¹

One thing that's important to remember is that in addition to all the dangerous bacteria we hear so much about, there are also many "good" bacteria that make it possible for us to live life as we know it. Bacteria help us digest food, make vitamins, and help our immune systems to keep the bad microbes out. Bacteria are single-celled organisms with one piece of DNA. How do these tiny organisms exert such powerful effects? One clue appears if we shift our focus from the size of a single bacterium to the sheer numbers present in an entire population. There are ten times more bacterial cells than human cells on a human! And there are one hundred times more bacterial genes than human genes on a human! Dr. Bassler wants to understand how these bacterial populations organized themselves to control human biology. The answer seems to lie in the fact that bacteria can communicate.

To study a bacterial communication system, Bassler and her group studied a bioluminescent marine bacterium called Vibrio fisheri. In dilute suspension, these bacteria do not release light.
However, when the bacteria reach a certain density, they all light up at the same time.

Vibrio fisheri lives mutualistically in the Hawaiian bobtail squid. This small nocturnal squid lives in shallow water off the coast of Hawaii. The squid cultivates cultures of Vibrio fisheri in a special light organ in its mantle. The bacteria allow the squid to counter-illuminate itself as an anti-predation device on bright moonlit nights. With sensors on its back to detect the level of ambient moonlight and shutters to control the amount of bioluminescent light that shines through its underside, the squid releases just enough light so that it doesn't create a shadow.

Bassler went on a quest for the molecular mechanism underlying the biology of this bacterium. She discovered that the bacteria make signaling hormones that are released into the environment. Each bacterial cell also has special receptors that "read" the hormone level in the environment. When enough of the signaling hormone is released, all the bacteria in the population respond at the same time. The nature of this group-sensing response varies in different species. In the case of Vibrio fisheri, all of the bacteria light up at the same time. Bassler calls the genes that control this process bacterial quorum-sensing genes because each member of the population plays a role. It's as if they all vote, and when they all vote - ta da! Bioluminescence. It turns out that all bacteria have communication systems like this.

Quorum-sensing genes underlie pathogenic infections. It's not that a few unhealthy microbes enter the body and then start secreting toxic substances. Rather, they multiply and multiply until a quorum is reached. Then this system of bacterial communication allows them to launch an attack simultaneously.

In terms of chemical structure, the communication molecules are related, but slight differences allow for species-specific communication. Bassler found that there is also a separate set of receptors and hormones for inter-species communication.

Dr. Bassler's discoveries could create a new way to treat bacterial infections that afflict human populations around the globe. Standard antibiotic treatments for harmful bacterial infections kill the bacteria by popping the cell membrane or making bacteria unable to replicate. Many bacteria have evolved resistance to this approach, so Bassler wondered what would happen if she attacked bacterial avenues of communication. Her group has made specific antagonists for both inter- and intra-species communication systems, with positive results. These antagonists could pave the way for a new class of compounds to control drug-resistant bacteria. In addition to her work on harmful bacteria, Dr. Bassler has also made pro-quorum-sensing molecules to enhance the work of mutualistic bacteria that benefit human life.

Bassler's work may have other interesting implications, including the idea that bacteria might have laid the groundwork for multicellularity! These organisms may have established the rules that eventually allowed for the development of multicellular orgnanisms such as ourselves.

To learn more about the bacterial genome, check out:
 http://www.nature.com/scitable/topicpage/Simple-Viral-and-Bacterial-Genomes-635

¹ http://www.ted.com/talks/lang/eng/bonnie_bassler_on_how_bacteria_communicate.html