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From "Eavesdropping on Bacterial Conversations" - Part II

In the last part, we covered a important way of how bacteria communicate to each other through quorum sensing. The LuxI-LuxR system describes an interesting signaling system used by bacteria of the same species.

Professor Bassler's laboratory is especially known for her work on autoinducer 2 (AI-2) system which allows for inter-species communication. The discovery of AI-2, and its fundamental workings were a true scientific detective stories with twists and turns, and its implications are still being researched today.

Work on a different luminescent marine bacterium, Vibrio harveyi, revealed that regulatory apparatus for creating luminescent was more complex. It relied on two separate input signals: AI-1 and AI-2 which were recogized by two membrane spanning receptor kinases LuxQ and LuxN respectively. How AI-1 and AI-2 are involved for luminescence may be less important here except to say that both signals need to be present. While more information could be inferred about AI-1 in V. harveyri because its structural similarity to that of V. fisherii's autoinducer, the real mystery was how AI-2 worked. Three key realizations helped to establish the role of AI-2.

1.) Firstly, the realization that the LuxS gene is involved in catalyzing the last step in the creation of homocysteine along with pro-AI-2, helped to solve the mystery that AI-2 is derived from the ribose structure that is part of S-adenosylhomocystein (SAH). Because the derivative structures of pro-AI-2 is highly unstable in the environment, the mystery remained what AI-2 looked like.
2.) However it was possible to use AI-2 as a bait for pull-down and purification of its receptor counter-part which was hypothesized to exist. The Bassler lab was successful in its effort to identify this receptor now known as LuxP. Ultimately, this led to the first co-crystal structure of LuxP and AI-2. The structure of AI-2 opened up a new question: What stabilized the furansyl borate diester bonds at the unassigned electron densities? The team spent months puzzling over this because although carbon's electron densities were very similar, carbon does not form stable diester bonds.
3.) To solve the puzzle of the unassigned electron densities, the team had to discover the possibility of boron, which is abundant in the oceans, being in the position of the electron. Further experiments, in which cultures of V. harveyi were optionally exposed to boron confirmed that boron is needed for bioluminescence.

The mystery was solved. But what is the significance of AI-2?

Take-Home Message: Bacterial Esperanto and what's so important about AI-2

It was soon discovered that homologues of receptors like LuxP existed in most other eubacterial species as well. Furthermore, as mentioned before, because AI-2 has such unstable diester bonds, many different isoforms exist and interconvert within a solution with AI-2. Much work in other species soon confirmed that different bacterial species recognize and bind different isoforms of AI-2. That is highly significant because whereas the LuxI-LuxR genes describe a highly specific form of communication. The AI-2 secreted by V. harveyi can interconvert into a molecule a different bacterial species can recognize and understand. Hence, bacterial Esperanto is born. Bioinformatics analysis revealed that AI-2 diverse roles in signaling are associated with formation of biofilms and virulance offering new avenues of attack in treating bacterial diseases. Reagents could be developed that would destroy AI-2 type signals. This could reduce the virulence of a particular bacterium. Professor Bassler remarked that in many ways, nature is already exploiting these forms of communications for its own survival. Over time, many bacterial species have developed a variety of ways to eavesdrop, change or mute another bacterial specie's messages for its own uses.

Professor Bassler concluded by reflecting on the nature of multicellular eukaryotic organisms: There is communication between cells of the same type, cells of different types, and even organisms of different types. If simple, modern bacteria can talk to each other and form complex structures in biofilms, the assumption is not too far off that perhaps the basis for multicellularity could have been born in the bacterial kingdom.

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