Say What? Bacterial Conversation Stoppers

Theinterspecies crosstalk and misdirection could have importantconsequences for human health, said Bonnie L. Bassler, an HHMIinvestigator at Princeton University whose study was published in theSeptember 29, 2005, issue of Nature. "The ability of cells tocommunicate with one another and the ability to interfere with thecommunication process could have consequences in niches containingcompeting species of bacteria or in niches where bacteria associatewith humans," Bassler said. "In the gut, you can imagine how the normalmicroflora might interfere with cell-cell communication to thwartbacterial invaders."

Using a chemical communication processcalled quorum sensing, bacteria converse among themselves to counttheir numbers and to get the population to act in unison. Asynchronized group of bacteria can mimic the power of a multi-cellularorganism, ready to face challenges too daunting for an individualmicrobe going it alone. Swelling populations trigger theirquorum-sensing apparatuses, which have different effects in differenttypes of bacteria. One species might respond by releasing a toxin,while another might cut loose from a biofilm and move on to anotherenvironment.

Each species of bacteria has a private language, butmost also share a molecular vernacular that Bassler's lab discoveredabout 10 years ago. A chemical signal called autoinducer-2 (AI-2),originating from the same gene in all bacteria, is released outside thecell to announce the cell's presence. Nearby bacteria take a localcensus by monitoring AI-2 levels and conduct themselves as thecircumstances warrant.

Researchers have speculated that AI-2 is auniversal language, and the new study from Bassler's lab is the firstto show those conversations taking place - and producing consequences —between co-mingling species.

Postdoctoral fellow Karina Xaviermixed E. coli, beneficial bacteria that live in the human gut, withVibrio harveyi, a marine species that naturally glows in the dark inthe presence of a crowd. In the test tube, AI-2 production by eitherspecies turned up the marine bacteria's light and turned on thequorum-sensing genes in E. coli. That confirmed what the scientistsalready suspected: the linguistic versatility of AI-2.

But thiscommon language does not guarantee the correct message gets through,the researchers discovered. In earlier work, Xavier had found that E.coli both produces and consumes AI-2. In this study, she set up anexperiment where multitudes of E. coli first produced then devouredenough AI-2 to dim the lights of the marine bacteria, essentiallyfooling the thriving oceanic gang into thinking its members were few,thereby terminating its quorum-sensing behaviors.

In a morerealistic encounter, Xavier mixed E. coli with V. cholerae, thecholera-causing bacteria that mixes with E. coli in human guts. Whencholera bacteria sense a quorum, they turn off their toxins and excretean enzyme to cut themselves loose from the intestine, so they can moveout of the body where they can infect another person. Here, E. colisquelched much of the quorum-sensing response of the cholera bacteria,although the effect was not as dramatic as with the marine bacteria.

"Thereal take-home point is the interference," Bassler said. "Consumptionof the signal could be a mechanism that allows one kind of bacteria toblock another kind of bacteria from counting how many neighbors theyhave and, in turn, properly controlling its behavior."

"Thisstudy moves us closer to really understanding how these interactionshappen in nature," Bassler said. "Bacteria can communicate betweenspecies, and they have evolved mechanisms to interfere with thecommunication. Probably this is but one of many cunning strategies theyhave for manipulating chemical communication. You can imagine that, inniche one, the bacteria we consider good guys might be using AI-2 andwinning. And unfortunately, in niche two, the bad guys might be usingAI-2 and winning."