Everett Peter Greenberg

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Everett Peter Greenberg
Born (1948-11-07) November 7, 1948 (age 75) [1]
New York City
United States [2]
Education Western Washington University (BA)
University of Iowa (MSc)
University of Massachusetts Amherst (PhD)
Known forResearch of quorum sensing
Spouse Caroline Harwood
Awards Shaw Prize in Life science and Medicine
Princess of Asturias Award for Technical and Scientific Research
Canada Gairdner International Award
Scientific career
Fields Microbiology
Institutions University of Washington
University of Iowa
Cornell University
Harvard University [3]
Thesis The biology of facultatively anerobic spirochetes  (1977)
Doctoral advisor Ercole Canale-Parola [4]

Everett Peter Greenberg (born November 7, 1948) is an American microbiologist. He is the inaugural Eugene and Martha Nester Professor of Microbiology at the Department of Microbiology of the University of Washington School of Medicine. [5] He is best known for his research on quorum sensing, and has received multiple awards for his work.

Contents

Early life and education

Greenberg was born in 1948 in New York City. When he was an infant, his family moved to San Francisco then to Seattle, where he finished high school. [4] [2] He became interested in biology, especially invertebrate biology, after a field trip his biology teacher organized. [2]

Greenberg was determined to study biology after a year at Everett Junior College (now Everett Community College), and, instead of the University of Washington which he thought was too big, opted for Western Washington University in Bellingham, Washington in 1966. [4] [2] He graduated with a BA in Biology in 1970. [3]

He discovered his passion for microbiology during his undergraduate years, so despite initially planning to pursue biochemistry for postgraduate study, he eventually went to the University of Iowa to conduct microbiology research, where he obtained his MSc in Microbiology in 1972. Greenberg then started his PhD at the University of Massachusetts Amherst, and received his PhD in 1977. [4]

Career

After obtaining his PhD, Greenberg spent time at Harvard University for postdoctoral work. [4] He joined the Department of Microbiology of Cornell University as an assistant professor in 1979, [4] and was promoted to associate professor in 1984. [3] Greenberg went to the Department of Microbiology of the University of Iowa as a professor in 1988, and returned to Seattle in 2005 when he joined the Department of Microbiology of the University of Washington as head of the department. [2] [6]

Outside of academia, Greenberg was an associate editor of the Annual Review of Microbiology from 1991 to 2001. [7]

Research

Before the 1960s and 70s, bacteria were thought to be independent organisms that do not communicate with one another. [8] [9] The first indication of inter-bacterial communication was reported by Alexander Tomasz in 1965, who found Streptococcus pneumoniae secretes a substance that allow other S. pneumoniae to take up foreign DNA. [10] Then in 1970, John Woodland Hastings discovered that Aliivibrio fischeri produced light and became bioluminescent under high cell density but not in diluted concentration, a phenomenon known as autoinduction. [11] The molecule that A. fischeri secretes for autoinduction is called an autoinducer, which was not identified until 1981.

In 1985, Greenberg reported that, instead of a complex mechanism, the autoinducer simply passively diffuses from one bacterial cell to another, [12] revealing one of the mechanisms of bacterial communication.

He switched course after moving to the University of Iowa, focusing on the luxR protein in A. fischeri; the protein is a transcription factor activated by the autoinducer. [13] Research by Greenberg's team confirmed the C-terminus of luxR binds DNA [14] while its N-terminus binds the autoinducer. [15]

In a seminal article in 1994, Greenberg, together with Claiborne (Clay) Fuqua and Stephen Winans, at the time both from Cornell University, coined the term quorum sensing to describe the behavior of autoinduced bioluminescence in A. fischeri and other bacterial species. [16]

Greenberg has also branched out from A. fischeri, collaborating with Barbara Iglewski at the University of Rochester to study quorum sensing in Pseudomonas aeruginosa , the infection of which is the primary cause of death in cystic fibrosis patients. The collaboration stemmed from Iglewski's discovery in 1991 of a P. aeruginosa gene coding for a transcription factor protein that controls the expression of genes which, in turn, control its virulence. The closest relative of the transcription factor, in terms of protein sequence, was the luxR protein. [17] This partnership led to the discovery of three quorum sensing signaling pathways in P. aeruginosa. [18]

His research in quorum sensing led Greenberg to study the phenomenon of biofilm, which is a high-density cluster of bacteria that attaches to each other and to surfaces and is embedded in an extracellular matrix. Notably, bacteria in biofilms are more resistant to antibiotics than their free-living counterparts. [13] In 1998, Greenberg, Iglewski, and J. William Costerton reported the link between quorum-sensing genes and biofilm formation, the first publication to show a genetic factor in biofilm structure. [19] Over the next years, he kept studying biofilms and their effects on diseases, discovering that lungs of cystic fibrosis patients are infected with biofilms, [20] and that iron is required for P. aeruginosa biofilm formation. [21]

Personal life

Greenberg met his wife, Caroline Harwood, during his PhD years at the University of Massachusetts Amherst. [2] They started dating when he was a postdoctoral researcher at Harvard University, and were married in 1984. [4] Harwood is currently also a professor at the Department of Microbiology of the University of Washington School of Medicine. [22]

Honors and awards

Related Research Articles

<span class="mw-page-title-main">Biofilm</span> Aggregation of bacteria or cells on a surface

A biofilm is an syntrophic community of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components, which are typically a polymeric combination of extracellular polysaccharides, proteins, lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms, they have been metaphorically described as "cities for microbes".

In biology, quorum sensing or quorum signaling (QS) is the ability to detect and respond to cell population density by gene regulation. Quorum sensing is a type of cellular signaling, and more specifically can be considered a type of paracrine signaling. However, it also contains traits of both autocrine signaling: a cell produces both the autoinducer molecule and the receptor for the autoinducer. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at which the resulting phenotypes will be most beneficial, especially for phenotypes that would be ineffective at low cell densities and therefore too energetically costly to express. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population. In a similar fashion, some social insects use quorum sensing to determine where to nest. Quorum sensing in pathogenic bacteria activates host immune signaling and prolongs host survival, by limiting the bacterial intake of nutrients, such as tryptophan, which further is converted to serotonin. As such, quorum sensing allows a commensal interaction between host and pathogenic bacteria. Quorum sensing may also be useful for cancer cell communications.

<i>Aliivibrio fischeri</i> Species of bacterium

Aliivibrio fischeri is a Gram-negative, rod-shaped bacterium found globally in marine environments. This species has bioluminescent properties, and is found predominantly in symbiosis with various marine animals, such as the Hawaiian bobtail squid. It is heterotrophic, oxidase-positive, and motile by means of a single polar flagella. Free-living A. fischeri cells survive on decaying organic matter. The bacterium is a key research organism for examination of microbial bioluminescence, quorum sensing, and bacterial-animal symbiosis. It is named after Bernhard Fischer, a German microbiologist.

<i>Vibrio harveyi</i> Species of bacterium

Vibrio harveyi is a Gram-negative, bioluminescent, marine bacterium in the genus Vibrio. V. harveyi is rod-shaped, motile, facultatively anaerobic, halophilic, and competent for both fermentative and respiratory metabolism. It does not grow below 4 °C. V. harveyi can be found free-swimming in tropical marine waters, commensally in the gut microflora of marine animals, and as both a primary and opportunistic pathogen of marine animals, including Gorgonian corals, oysters, prawns, lobsters, the common snook, barramundi, turbot, milkfish, and seahorses. It is responsible for luminous vibriosis, a disease that affects commercially farmed penaeid prawns. Additionally, based on samples taken by ocean-going ships, V. harveyi is thought to be the cause of the milky seas effect, in which, during the night, a uniform blue glow is emitted from the seawater. Some glows can cover nearly 6,000 sq mi (16,000 km2).

<i>N</i>-Acyl homoserine lactone Class of chemical compounds

N-Acyl homoserine lactones are a class of signaling molecules involved in bacterial quorum sensing, a means of communication between bacteria enabling behaviors based on population density.

<i>Pseudomonas aeruginosa</i> Species of bacterium

Pseudomonas aeruginosa is a common encapsulated, Gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. P. aeruginosa is able to selectively inhibit various antibiotics from penetrating its outer membrane - and has high resistance to several antibiotics, according to the World Health Organization P. aeruginosa poses one of the greatest threats to humans in terms of antibiotic resistance.

Autoinducers are signaling molecules that are produced in response to changes in cell-population density. As the density of quorum sensing bacterial cells increases so does the concentration of the autoinducer. Detection of signal molecules by bacteria acts as stimulation which leads to altered gene expression once the minimal threshold is reached. Quorum sensing is a phenomenon that allows both Gram-negative and Gram-positive bacteria to sense one another and to regulate a wide variety of physiological activities. Such activities include symbiosis, virulence, motility, antibiotic production, and biofilm formation. Autoinducers come in a number of different forms depending on the species, but the effect that they have is similar in many cases. Autoinducers allow bacteria to communicate both within and between different species. This communication alters gene expression and allows bacteria to mount coordinated responses to their environments, in a manner that is comparable to behavior and signaling in higher organisms. Not surprisingly, it has been suggested that quorum sensing may have been an important evolutionary milestone that ultimately gave rise to multicellular life forms.

<span class="mw-page-title-main">Lactonase</span> Class of enzymes

Lactonase (EC 3.1.1.81, acyl-homoserine lactonase; systematic name N-acyl-L-homoserine-lactone lactonohydrolase) is a metalloenzyme, produced by certain species of bacteria, which targets and inactivates acylated homoserine lactones (AHLs). It catalyzes the reaction

<span class="mw-page-title-main">Autoinducer-2</span> Chemical compound

Autoinducer-2 (AI-2), a furanosyl borate diester or tetrahydroxy furan, is a member of a family of signaling molecules used in quorum sensing. AI-2 is one of only a few known biomolecules incorporating boron. First identified in the marine bacterium Vibrio harveyi, AI-2 is produced and recognized by many Gram-negative and Gram-positive bacteria. AI-2 arises by the reaction of 4,5-dihydroxy-2,3-pentanedione, which is produced enzymatically, with boric acid and is recognized by the two-component sensor kinase LuxPQ in Vibrionaceae.

Roberto Kolter is Professor of Microbiology, Emeritus at Harvard Medical School, an author, and past president of the American Society for Microbiology. Kolter has been a professor at Harvard Medical School since 1983 and was Co-director of Harvard's Microbial Sciences Initiative from 2003-2018. During the 35-year term of the Kolter laboratory from 1983 to 2018, more than 130 graduate student and postdoctoral trainees explored an eclectic mix of topics gravitating around the study of microbes. Kolter is a fellow of the American Association for the Advancement of Science and of the American Academy of Microbiology.

<span class="mw-page-title-main">Rhamnolipid</span> Chemical compound

Rhamnolipids are a class of glycolipid produced by Pseudomonas aeruginosa, amongst other organisms, frequently cited as bacterial surfactants. They have a glycosyl head group, in this case a rhamnose moiety, and a 3-(hydroxyalkanoyloxy)alkanoic acid (HAA) fatty acid tail, such as 3-hydroxydecanoic acid.

Interspecies quorum sensing is a type of quorum sensing in which bacteria send and receive signals to other species besides their own. This is accomplished by the secretion of signaling molecules which trigger a response in nearby bacteria at high enough concentrations. Once the molecule hits a certain concentration it triggers the transcription of certain genes such as virulence factors. It has been discovered that bacteria can not only interact via quorum sensing with members of their own species but that there is a kind of universal molecule that allows them to gather information about other species as well. This universal molecule is called autoinducer 2 or AI-2.

Acyl-homoserine-lactone synthase is an enzyme with systematic name acyl-(acyl-carrier protein):S-adenosyl-L-methionine acyltranserase . This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Bioluminescent bacteria</span>

Bioluminescent bacteria are light-producing bacteria that are predominantly present in sea water, marine sediments, the surface of decomposing fish and in the gut of marine animals. While not as common, bacterial bioluminescence is also found in terrestrial and freshwater bacteria. These bacteria may be free living or in symbiosis with animals such as the Hawaiian Bobtail squid or terrestrial nematodes. The host organisms provide these bacteria a safe home and sufficient nutrition. In exchange, the hosts use the light produced by the bacteria for camouflage, prey and/or mate attraction. Bioluminescent bacteria have evolved symbiotic relationships with other organisms in which both participants benefit close to equally. Another possible reason bacteria use luminescence reaction is for quorum sensing, an ability to regulate gene expression in response to bacterial cell density.

The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae, the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda.

Barbara Hotham Iglewski was an American microbiologist. She was director of international programs at the University of Rochester Medical Center where she was a professor of microbiology and immunology.

Karine Gibbs is a Jamaican American microbiologist and immunologist and an associate professor in the Department of Plant and Microbial Biology at the University of California, Berkeley. Gibbs’ research merges the fields of sociomicrobiology and bacterial cell biology to explore how the bacterial pathogen Proteus mirabilis, a common gut bacterium which can become pathogenic and cause urinary tract infections, identifies self versus non-self. In 2013, Gibbs and her team were the first to sequence the genome of P. mirabilis BB2000, the model organism for studying self-recognition. In graduate school at Stanford University, Gibbs helped to pioneer the design of a novel tool that allowed for visualization of the movement of bacterial membrane proteins in real time. In 2020, Gibbs was recognized by Cell Press as one of the top 100 Inspiring Black Scientists in America.

Kalai Mathee is a professor at Florida International University, joint editor-in-chief of the Journal of Medical Microbiology, and an elected fellow of the American Academy of Microbiology. She is known for her research on bacterial infections caused by Pseudomonas aeruginosa.

<i>Pseudomonas</i> quinolone signal Molecule to signal group actions in cells

The molecule 2-heptyl-3-hydroxy-4-quinolone, also named the Pseudomonas quinolone signal (PQS), has been discovered as an intracellular link between the two major quorum sensing systems of P. aeruginosa; the las and rhl systems. These systems together control expression of virulence factors and play a major role in the formation of biofilms in Pseudomonas aeruginosa. P. aeruginosa is a gram-negative bacteria and opportunistic human pathogen that can cause serious and sometimes fatal infections in humans. Similar to other bacterial species, P. aeruginosa uses quorum sensing (QS) systems to communicate between cells in a population. This allows coordination of gene expression in a population based on changing cell densities, abundance of nutrients, and other environmental factors.

References

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  14. ↑ Choi, S. H.; Greenberg, E. P. (1991). "The C-terminal region of the Vibrio fischeri LuxR protein contains an inducer-independent lux gene activating domain". Proceedings of the National Academy of Sciences. 88 (24): 11115–11119. Bibcode:1991PNAS...8811115C. doi: 10.1073/pnas.88.24.11115 . PMC   53084 . PMID   1763027.
  15. ↑ Hanzelka, Brian L.; Greenberg, E. P. (1995). "Evidence that the N-terminal region of the Vibrio fischeri LuxR protein constitutes an autoinducer-binding domain". Journal of Bacteriology. 177 (3): 815–817. doi: 10.1128/jb.177.3.815-817.1995 . PMC   176662 . PMID   7836318.
  16. ↑ Fuqua, W. Claiborne; Winans, Stephen C.; Greenberg, E. Peter (1994). "Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators". Journal of Bacteriology. 176 (2): 269–275. doi: 10.1128/jb.176.2.269-275.1994 . PMC   205046 . PMID   8288518.
  17. ↑ Gambello, Michael J.; Iglewski, Barbara H. (1991). "Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression". Journal of Bacteriology. 173 (9): 3000–3009. doi: 10.1128/jb.173.9.3000-3009.1991 . PMC   207884 . PMID   1902216.
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  20. ↑ Singh, Pradeep K.; Schaefer, Amy L.; Parsek, Matthew R.; Moninger, Thomas O.; Welsh, Michael J.; Greenberg, E. P. (2000). "Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms". Nature. 407 (6805): 762–764. Bibcode:2000Natur.407..762S. doi:10.1038/35037627. PMID   11048725. S2CID   4372096 . Retrieved August 21, 2023.
  21. ↑ Banin, Ehud; Vasil, Michael L.; Greenberg, E. Peter (2005). "Iron and Pseudomonas aeruginosa biofilm formation". Proceedings of the National Academy of Sciences. 102 (31): 11076–11081. Bibcode:2005PNAS..10211076B. doi: 10.1073/pnas.0504266102 . PMC   1182440 . PMID   16043697.
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