It’s a quorum. Bonnie Bassler awarded 2012 L’ORÉAL-UNESCO Award in Life Sciences

Bacteria can talk. Yes. Talk. These unicellular, primitive creatures have their own language. They secret chemical words to their environment, where their neighbors can listen, comprehend and react to those messages.

This bacterial communication is called quorum sensing (QS).

Although the first discoveries in the field of bacterial communication where made more than 40 years ago in the marine bacterium Vibrio fisheri (1), they simply did not have the quorum to be heard. Until Bonnie Bassler came along.
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Thanks to Bonnie and her colleagues, today, microbiology courses throughout the world include QS as part of its syllabus.

And the story of QS is not just a tale for scientists, it affects all of our lives.

Like many other discoveries in science, this one too began by a stroke of luck.

During her PhD, Bonnie Bassler attended her first ever conference in Baltimore, where she quite accidentally heard the one-in-a-ten-year talk of a reclusive geneticist, Professor Mike Silverman, who reported his studies on bioluminescence in the marine bacterium V. fisheri. Being a chemist, she admits to not understanding much of what Silverman was talking about, yet she knew, this is what she wanted to do. ‘I have to work on this or I’m going to quit science!”‘ she remember saying to herself.

Bassler had begun her scientific career at the University of California at Davis. She joined the lab of professor Fredrick Troy, (Biochemistry and Molecular Medicine) hoping to work on one of his viral projects dealing with Epstein-Barr virus and its relationship to cancer, thinking at that time, that viruses are important and bacteria are not. Much to her disappointment professor Troy handed her a project working on bacterial carbohydrates. And this was where she first learned to know bacteria.

She then crossed the country for her PhD studies at the lab of professor Saul Roseman in the Johns Hopkins University (Baltimore, MD). There, she continued to study bacterial-carbohydrate interaction.

As she was about to complete her doctorate, the conference in Baltimore took place. Professor Mike Silverman, the geneticist, had been studying a phenomenon first described decades earlier by National Academy of Science member and Harvard University (Cambridge, MA) professor J. Woodland Hastings. Hastings discovered QS in the bioluminescent marine bacteria V. fischeri and its relative V. harveyi (1, 2). He coined the term “autoinducer” to describe the chemical messenger, a homoserine lactone (HSL), that the microorganisms used to communicate and to produce light.

Silverman ended his talk saying “‘Don’t you see, these bacteria are communicating with this molecule. They are acting multicellular.’” At the end of his talk, Bassler steamed to the podium and ask Silverman for a job. Much to her surprise, he offered her a postdoc position right there. She packed her stuff and returned to California and began studying bioluminescence in the marine bacterium V. harveyi.

During her postdoc, Bassler defined the QS circuit of V. harveyi. She showed that, like V. fischeri, V. harveyi communicated with other members of its species by using a chemical signal called an HSL autoinducer (3). The marine bacteria secrete this autoinducer into their environment. As long as bacteria are in low numbers in dilute suspension the autoinducer is washed away and no act is being taken, but when bacteria replicate and grow in number, the concentration of the autoinducer molecule also increases in the surrounding. When it reaches a certain threshold it is sensed by the bacteria and gives it an indication of its own population size. They then respond simultaneously by activating their light genes to produce bioluminescence. As Bassler puts it so nicely in her TED talk, “they vote with these chemical votes, the votes get counted and then everybody responds to the vote”.

Bassler also discovered that V. harveyi had more than one molecule for QS; she called this additional molecule autoinducer-2 (AI-2) (3, 4), and the original, found by Hastings, became autoinducer-1 (AI-1).

Soon after her discovery of AI-2, in 1994 Bassler decamped the La Jolla institute for a tenure-track position at Princeton. Tom Silhavy was head of the search committee at Princeton that hired Bonnie Bassler said “he just had a feeling”… “It’s hard to know how a newly hired faculty member is going to do in their first independent position, so you have to trust your instincts”… 18 years and about 80 high-impact papers later, he knows his instincts were right. “She’s now more famous than all the rest of us combined”, he said.

Bassler flew to Princeton with all her belongings and her sole companion, a cat. When she arrived at Princeton, she had nothing but empty rooms in the Lewis Thomas Laboratory building and a budget for filling them.

Bassler continued her research on QS in the marine bacterium V. harveyi in Princeton only to discover that QS is a lot bigger then what she had realized.

So… you can legitimately ask what’s all the fuss about understanding the genetic and chemical basis of how marine bacteria talk to each other and produce light?

It turns out that bacteria use QS not only for bioluminescence but also for many other important traits, most important of which, virulence (5-8). Actually, in this regard bacteria act very similar to us; if you would want to do something that’s beyond your reach as an individual, you’d talk to some other guys, get the necessary quorum, and then carry it together. Bacteria use exactly the same strategy, or as Bonnie puts it, “they are just too small to have an impact on the environment if they simply act as individuals”.
Thinking of it, bacteria are microscopic creatures, and probably their only chance to overcome a huge host is by acting together. So they count them self up and only when the right amount of cells is present they launch their virulence attack to take over their host.

And this simple realization, has huge implications for human health.

Several years after Bassler’s discovery of the second QS system in V. harveyi, she discovered that this additional QS system is wide spread in bacteria and that unlike the first QS system, these signals were common and shared by all bacteria. Meaning that different species and even different genera of bacteria can communicate with one another with one universal chemical language, the “bacterial esperanto” as Bassler calls it (9, 10). Considering that 10 years earlier scientists did not believe that bacteria can even communicate with their own species, this discovery was overwhelming. It was actually so revolutionary that in 2002 she was awarded with the prestigious fellowship of the MacArthur Foundation, anointing her with the “genius” tag.

The ubiquiitousity of QS in the bacterial kingdom and its importance, surpassed even Bassler’s imagination admitting; “we always knew we were working on something bigger than bioluminescence, but we didn’t think it would be what it turned out to be. It’s just been so much better”

Further discoveries in other bacteria revealed that all bacteria are using one form, or another of QS to coordinate group behavior (5-8). This was a major discovery, because it meant that this in not an anomaly restricted to harmless marine bacteria that communicate to produce light, but it also used by the most deadly human pathogen to achieve successful host infection.

So… if we can break the code, eavesdrop the conversation, manipulate the information, we could interfere with bacterial communication to coordinate their attack and thereby prevent disease. A whole new class of bacterial antibiotics. Unlike most common antibiotics, aimed at killing bacteria, a practice which promotes the development of antibiotic resistant strains, this new class of antibiotics would aim to disrupt bacterial communication. Simply preventing bacteria from talking to, or hearing each other and activating their vicious group behaviors.

Bassler have already discovered QS antagonist which were shown to disrupt bacterial pathogenesis, preventing it from killing its host, in this case the model organism, Caenorhabditis elegans, a microscopic warm (11), opening a window to this potentially new antibiotic.

Bassler, a pioneer in the field of bacterial communication, a Howard Hughes scholar and a member of the National Academy of Sciences, wants to put things in perspective when she says, that basic science is great, but she would really want to do something practical, “I want to actually, in my life time, help people”, putting the emphasis on generating knowledge for the purpose of solving our problems.

Bassler is richly deserving of the 2012 L’ORÉAL-UNESCO Award in Life Sciences “For understanding chemical communication between bacteria and opening new doors for treating infections”. She is still very much engaged in elucidating the secretes of bacterial communication and finding ways to manipulate this knowledge for the benefit of all of us.

Written by Ofir Bahar and Pamela Ronald

Bibliography
1. Hastings JW & Nealson KH (1977) Bacterial bioluminescence. Annu Rev Microbiol 31:549-595.
2. Nealson KH, Platt T, & Hastings JW (1970) Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 104:313-322.
3. Bassler BL, Wright M, Showalter RE, & Silverman MR (1993) Intercellular signalling in Vibrio harveyi: sequence and function of genes regulating expression of luminescence. Mol Microbiol 9:773-786.
4. Bassler BL, Wright M, & Silverman MR (1994) Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway. Mol Microbiol 13:273-286.
5. Miller MB, Skorupski K, Lenz DH, Taylor RK, & Bassler BL (2002) Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110(3):303-314.
6. Dong YH, Xu JL, Li XZ, & Zhang LH (2000) AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora. P Natl Acad Sci USA 97:3526-3531.
7. Rothfork JM, et al. (2004) Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: New role for the NADPH oxidase in host defense. P Natl Acad Sci USA 101(38):13867-13872.
8. Guiral S, Mitchell TJ, Martin B, & Claverys J-P (2005) Competence-programmed predation of noncompetent cells in the human pathogen Streptococcus pneumoniae: Genetic requirements. P Natl Acad Sci USA 102(24):8710-8715.
9. Surette MG, Miller MB, & Bassler BL (1999) Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: A new family of genes responsible for autoinducer production. Proceedings of the National Academy of Sciences of the United States of America 96(4):1639-1644.
10. Chen X, et al. (2002) Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415(6871):545-549.
11. Swem LR, et al. (2009) A quorum-sensing antagonist targets both membrane-bound and cytoplasmic receptors and controls bacterial pathogenicity. Molecular Cell 35(2):143-153

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Pamela Ronald is Professor of Plant Pathology at the University of California, Davis, where she studies the role that genes play in a plant’s response to its environment. Her research focuses on the genetics of rice. With her husband, she co-wrote Tomorrow's Table:organic farming, genetics and the future of food. She writes a blog of the same name.


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