FRANKFURT am MAIN. Two American scientists, Bonnie L. Bassler and Michael R. Silverman, receive the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize, which is endowed with 120,000 €.
Bassler is Professor at Princeton University and a Howard Hughes Medical Institute Investigator, Michael R. Silverman is Emeritus Professor of the Agouron Institute in La Jolla.
The two researchers are honoured for their ground-breaking discoveries concerning bacterial "quorum sensing", which refers to sophisticated systems of cell-to-cell communication that bacteria use to coordinate group behaviors.
The award ceremony in St. Paul's Church, which is traditionally held on March 14, Paul Ehrlich's birthday, has been postponed due to the Coronavirus pandemic. Instead, Bassler and Silverman will receive the award at the ceremony in 2022.
"Silverman and Bassler have shown that, as for multicellular organisms, collective behavior is the rule among bacteria, rather than the exception," wrote the Scientific Council in substantiating its decision. "Bacteria talk to each other, they eavesdrop on other bacteria, and they may even join forces. But: This ubiquitous chitchat, whose molecular underpinnings were discovered by Bassler and Silverman, also represents a previously unappreciated Achilles' heel in combating harmful microbes. Instead of killing bacteria with antibiotics, substances may be developed that interfere with bacterial communication effectively reducing their collective fitness. The prize-winners' research thus has considerable relevance for medicine".
Bacteria are extremely communicative. They send and receive chemical messages to find out whether they are alone or if additional members of their or other species are present in the vicinal community. To take a census of cell numbers, bacteria produce and release chemical signal molecules that accumulate in step with increasing cell numbers.
When a threshold level of the chemical signal is achieved, the bacteria detect its presence. In response to it, in unison, bacteria undertake behaviors that are only productive when carried out in synchrony by the group, but not when enacted by a single bacterium acting in isolation. This chemical communication process is called quorum sensing and it controls hundreds of collective activities across the bacterial kingdom.
In the 1980s, Silverman discovered the first quorum-sensing circuit in the bioluminescent marine bacterium Vibrio fischeri. He identified the genes and proteins enabling production and detection of the extracellular signal molecule.
He defined how the components functioned to promote collective behavior. In the case of Vibrio fischeri, group-wide behavior is the production of blue-green bioluminescence.
Today, we know that quorum sensing is the norm in the bacterial world. Indeed, there are thousands of bacterial species that possess genes nearly identical to those discovered by Silverman. In all of these cases, these components allow bacteria to engage in group behaviors.
In the early 1990s, Bonnie Bassler proved that bacteria were "multilingual" and that they conversed with multiple chemical signal molecules. One communication molecule that Bassler discovered and named autoinducer- 2 enables bacteria to communicate across species boundaries.
She went on to demonstrate that bacteria use quorum-sensing-mediated communication to differentiate self from other, showing that a sophisticated trait thought to be the purview of higher organisms, in fact, evolved in bacteria billions of years ago.
In recent years, Bassler has shown that quorum sensing transcends kingdom boundaries as viruses and host cells, including human cells, engage in this ubiquitous chit-chat.
She and other researchers also demonstrated that pathogenic bacteria rely on quorum sensing to be virulent. Bassler developed anti-quorum-sensing strategies that, in animal models, halt infection from bacterial pathogens of global significance.
The full significance of the discoveries of the two laureates for microbiology and medicine has only recently been recognized. Decades of meticulous and painstaking work, showed that essentially all bacteria master the art of cell-to-cell communication. What began with work on Vibrio fischeri and Vibro harveyi led to a fundamental change in perspective in bacteriology, and now opens up new and unprecedented opportunities in dealing with antibiotic resistance".
Thomas Boehm, Professor and Director, Chairman of the Scientific Council, Max Planck Institute for Immunobiology and Epigenetic
Short biography Professor Dr. Bonnie L. Bassler Ph.D. (58).
Bonnie Bassler is a microbiologist. She studied biochemistry at the University of California at Davis and received her Ph.D. from the Johns Hopkins University in Baltimore. She joined the laboratory of Michael Silverman at the Agouron Institute in La Jolla as a postdoctoral fellow in 1990.
She has been at Princeton University since 1994. Bonnie Bassler is a member of the National Academy of Sciences, the National Academy of Medicine, and the Royal Society. She is a researcher at the Howard Hughes Medical Institute and Squibb Professor and Chair of the Department of Molecular Biology at Princeton University. President Obama appointed her to a six-year term on the United States National Science Board. She has received more than twenty prestigious national and international awards.
Short biography Professor Michael R. Silverman, Ph.D. (77).
Michael Silverman is a microbiologist. He studied chemistry and bacteriology at the University of Nebraska at Lincoln and received his Ph.D. in 1972 from the University of California at San Diego. During the period from 1972-1982, Silverman made seminal contributions to the understanding of bacterial motility and chemotaxis. From 1982 until his retirement, he worked at the Agouron Institute in La Jolla, of which he is a co-founder.
The Paul Ehrlich and Ludwig Darmstaedter prize
The Paul Ehrlich and Ludwig Darmstaedter Prize is traditionally awarded on Paul Ehrlich's birthday, March 14, in the Paulskirche, Frankfurt. It honors scientists who have made significant contributions in Paul Ehrlich's field of research, in particular immunology, cancer research, microbiology, and chemotherapy.
The Prize, which has been awarded since 1952, is financed by the German Federal Ministry of Health, the State of Hesse, the German association of research-based pharmaceutical company vfa e.V. and specially earmarked donations from the following companies, foundations and organizations: Else Kröner-Fresenius-Stiftung, Sanofi-Aventis Deutschland GmbH, C.H. Boehringer Pharma GmbH & Co.
KG, Biotest AG, Hans und Wolfgang Schleussner-Stiftung, Fresenius SE & Co. KGaA, F. Hoffmann-LaRoche Ltd., Grünenthal GmbH, Janssen-Cilag GmbH, Merck KGaA, Bayer AG, Holtzbrinck Publishing Group, AbbVie Deutschland GmbH & Co. KG, die Baden-Württembergische Bank, B. Metzler seel. Sohn & Co. and Goethe-Universität. The prizewinners are selected by the Scientific Council of the Paul Ehrlich Foundation.
The Paul Ehrlich foundation
The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president of the German Research Foundation, who also appoints the elected members of the Scientific Council and the Board of Trustees.
The Chairman of the Scientific Council is Professor Thomas Boehm, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.
Bacterial chit-chat
Bacteria communicate with each other and coordinate behavior to achieve feats that could not be accomplished by a single bacterium acting alone. Even viruses infecting bacterial cells and cells of higher organisms, including human cells, tune into this ubiquitous bacterial chit-chat. Manipulating this polyphony offers new opportunities to defend ourselves against bacterial pathogens by disrupting their cell-to-cell communication capabilities.
How does an individual bacterium inform itself and respond appropriately to a crowded and diverse community? Are there other bacterial species around? If so, are they friend or foe? What about organisms from other domains like viruses and humans?
Bacteria, earth's most ancient living organisms, gather information about the neighbourhood to work out whether or not it makes sense to participate in collective activities. In so doing, groups of bacteria reap benefits that are not possible for a single bacterium acting in isolation.
To achieve this feat, bacteria use chemical communication, a process called quorum sensing, which informs them about the numbers and identities of other organisms in the vicinity.
This year's Paul Ehrlich and Ludwig Darmstaedter Prize honours two American scientists for their discovery of the molecular basis of bacterial cell-to-cell communication: Professor Michael R. Silverman Ph.D., Emeritus of the Agouron Institute in La Jolla CA, and Professor Bonnie L. Bassler Ph.D. of Princeton University and the Howard Hughes Medical Institute.
Bacteria act collectively
Prior to the discovery of cell-to-cell communication in bacteria, these ancient single cell organisms were viewed as loners, whose primitive lifestyles consisted primarily of dividing and dispersing their progeny.
The ability to communicate with their own kind, other bacterial species, viruses, and host organisms was unimaginable. Today, thanks to the groundbreaking research of Silverman and Bassler, we know that such sophisticated communication abilities are the norm in the bacterial world.
The discoveries began in the 1970s with an observation made by the late American scientist Woody Hastings. He showed that the bioluminescent marine bacterium Vibrio fischeri glows in the dark only when it has grown to a particular cell density.
But how did Vibrio fischeri "know" when to produce light and when to remain dark? Hastings and his mentees showed that Vibrio fischeri produces and releases a molecule, that the team termed an "autoinducer", that accumulates in the environment as the bacteria increase in cell number. When the autoinducer reaches a threshold level, it alerts the Vibrio fischeri bacteria that they have neighbours around, and in unison, all of the bacteria turn on light.
The molecular mechanism underlying the synchronous production of light by Vibrio fischeri remained mysterious until Michael Silverman, together with his graduate student JoAnne Engebrecht, became fascinated by the possibility of collective behaviors in bacteria.
They reasoned that by using molecular genetic techniques, they could reconstruct the Vibrio fischeri bioluminescence system in laboratory Escherichia coli and identify the genes and proteins controlling light production. Crucially, this strategy revealed the enzyme required to make the autoinducer molecule and the receptor protein whose job is to monitor the autoinducer buildup, and in response, initiate the population-wide production of blue-green light.
Silverman's experiment delivered the first molecular mechanism underlying a bacterial group behavior. Today, there are thousands of bacterial species known to possess genes nearly identical to those discovered by Silverman. In all of these cases, these components allow the bacteria to engage in group behaviors. This chemical communication process is now called quorum sensing.
Friend or foe?
Bonnie Bassler joined Silverman's laboratory in 1990 after completing her doctoral research. She was curious whether there could be more to cell-cell communication than the components discovered by Silverman in Vibrio fischeri. Bassler launched her investigations in Silverman's lab with a close relative of Vibrio fischeri, a light-producing bacterium named Vibrio harveyi that was known to have a more varied and exotic lifestyle than Vibrio fischeri.
Bassler and Silverman discovered that Vibrio harveyi possessed multiple quorum-sensing systems, and that more than one autoinducer is used for communication. In her independent career, Bassler identified the new Vibrio harveyi molecule and she named it autoinducer-2.
She found that autoinducer-2 is broadly made in the bacterial world. Remarkably, rather than inform bacteria of their own cell numbers, autoinducer-2 informs them about the cell count of other bacterial species in the vicinity.
Thus, Bassler showed that bacteria can converse across species boundaries using a universal language akin to Esperanto. This discovery revealed that, similar to cells in higher organisms, bacteria differentiate self from other. Bassler went on to demonstrate that it is the norm for bacteria to be "multilingual" and they commonly use combinations of several autoinducers to take a census of self, related kin, and non kin. Based on the information they garner from these chemical blends, and whether neighbouring bacteria are allies or enemies, bacteria appropriately enact a wide variety of offensive or defensive collective behaviors.
More recently, Bassler discovered that viruses eavesdrop on bacterial quorum sensing and human gut cells team up with microbiome bacteria, the community of bacteria that naturally resides in the intestine, to synthesise yet another new quorum-sensing molecule which is used to defend both the human and the microbiome community against invading pathogens. Thus, Bassler's work has shown that quorum sensing transcends kingdom boundaries as viruses and higher organisms, including human hosts, participate in these chemical conversations.
High medical relevance
Silverman and Bassler's work revolutionized the understanding of microbial communities, a ground-breaking achievement whose fundamental relevance is now accepted after decades of persistent work combined with excellent publications.
For decades after the initial discoveries, it was thought that quorum sensing was simply an idiosyncratic phenomenon restricted to obscure bioluminescent bacteria. However, what appeared to be an isolated curiosity turned out to be universal in the bacterial world.
The medical importance of these findings is now obvious. Bassler and other researchers showed that quorum sensing controls virulence in disease-causing bacteria. Bassler was the first to make anti-quorum-sensing strategies and successfully use them in animal models to halt infection by pathogens of global relevance.
Such findings suggest that it may be possible to develop wholly-new and urgently needed anti-microbial therapies that interfere with quorum sensing rather than kill bacteria as do traditional antibiotics. Therefore, the laureates are not only honoured for their fundamental discoveries with respect to the molecular nature of cell-to-cell communication of bacteria, but they are also recognized for the enormous potential of their research in treating infections caused by bacteria resistant to conventional antibiotics.
Considerable efforts are now being invested to turn these concepts into practice. Lastly, quorum-sensing modulation strategies could also be deployed to harness beneficial bacterial processes, for example, to enhance the healthful effects of microbiome bacteria that reside in the human gut or on the skin.
Professor Nancy Ip: Pioneering New Paths in Neurodegenerative Therapy