Roberto Kolter | |
---|---|
Born | 1953 Guatemala |
Known for | Biofilms, stationary phase, antibiotic biosynthesis |
Scientific career | |
Fields | Microbiology, molecular genetics, chemical ecology, molecular microbiology, microbial ecology |
Institutions | Harvard Medical School |
Doctoral advisor | Donald Helinski |
Other academic advisors | Charles Yanofsky |
Website | http://gasp.med.harvard.edu/ |
Roberto Kolter is Professor of Microbiology, Emeritus at Harvard Medical School, an author, and past president of the American Society for Microbiology. [1] [2] Kolter has been a professor at Harvard Medical School since 1983 and was Co-director of Harvard's Microbial Sciences Initiative from 2003-2018. [3] During the 35-year term of the Kolter laboratory from 1983 to 2018, more than 130 graduate students and postdoctoral trainees explored an eclectic mix of topics gravitating around the study of microbes. [4] [5] Kolter is a fellow of the American Association for the Advancement of Science and of the American Academy of Microbiology. [6]
As Professor Emeritus, Kolter has continued his involvement in science by communicating microbiology to scientific and general audiences. [7] [8] Since 2016, Kolter has been co-blogger (with Moselio Schaechter) of the popular microbiology blog, Small Things Considered . [9] From 2014 to 2018, Kolter and Scott Chimileski developed two exhibitions at the Harvard Museum of Natural History: World in a Drop, open in 2017, and Microbial Life , open through 2020. [10] In parallel, Chimileski and Kolter wrote the book Life at the Edge of Sight: A Photographic Exploration of the Microbial World (Harvard University Press, 2017). [7] [11] [12] During a 2018 interview at EAFIT University in Colombia, Kolter explained that he is “in a more contemplative phase of his career," adding that he is enjoying "being able to exercise a little more the 'Ph' (Philosophy) of my PhD". [8]
Kolter was born and raised in Guatemala. [9] He received a Bachelor of Science degree in Biology from Carnegie Mellon University in 1975 and a PhD in Biology from the University of California, San Diego in 1979. [7] He was then a Helen Hay Whitney Postdoctoral Fellow at Stanford University with Charles Yanofsky from 1980 to 1983. [7] Kolter joined the faculty at Harvard Medical School as an Assistant Professor in 1983, was promoted to Associate Professor in 1989, Professor in 1994, and became Professor Emeritus upon his retirement from running a research laboratory in 2018. [7]
The research activities of Kolter's laboratory at Harvard Medical School from 1983 to 2018 encompassed several major parallel lines of investigation and spanned many interrelated subfields of microbiology. [5] [7] The overarching theme of the laboratory was to use genetic approaches to study physiological processes (and associated emergent properties) that bacteria have evolved to respond to stressful conditions in the environment, like starvation or limited nutrients, or as a result of ecological interactions with other living organisms. [7] [13] The eclectic nature of Kolter's research program was also a result of his policy of encouraging postdoctoral scientists to explore independent interests. [5] In an interview with Nature in 2015, Kolter was quoted on this mentorship style: "I let postdocs explore what they want to explore, as long as it is within the sphere of my interest." [5]
In total, Kolter has co-authored over 250 research and other scholarly articles which together have been cited over 50,000 times. [7] [14] [15] Kolter's research group was influential in the study of bacterial transport systems known as ABC exporters, published some of the earliest examples of experimental evolution through investigations of the stationary phase of bacterial growth, [7] [16] [17] [18] and was foundational in genetic studies of bacteria adhered to surfaces (living within communities called biofilms). [19] [20] The lab popularized the concept of bacterial biofilm formation as developmental or multicellular microbial processes, [21] [22] [23] and pioneered genetic studies of cellular differentiation, signaling, [24] and division of labor in bacteria. [25] [26] [27] In addition, his group has worked on other aspects of bacterial physiology, [28] the domestication of lab strains of bacteria, [29] microbiome ecology, [30] [31] [32] [33] interactions between plants and bacteria, [34] [35] [36] bacterial respiration processes, [37] and bioactive compound discovery. [38] [39] [40] [41]
Some of Kolter's significant scientific contributions are categorized below in chronological order.
As a graduate student, Kolter's research provided early evidence for what was called the "replicon hypothesis," proposed by Jacob, Brenner and Cuzin in 1962. [42] His work defined an origin of DNA replication that led to the development of many suicide cloning vectors still in use today.
As a new faculty member at Harvard Medical school in the 1980s, Kolter's research group made use of Escherichia coli as a model organism for understanding the molecular genetics of antibiotic biosynthesis. During the course of this work the group was among the first to characterize ABC exporters, today known to be one of the most important membrane protein systems that move molecules across the cell membrane.
In the late 1980s, Kolter's research group became interested in bacteria living in the stationary phase of the growth cycle, a state more like the natural conditions that bacteria experience in environments outside of the laboratory. [43] The group discovered regulatory systems exclusive to cells in this non-growing state and found that mutants with greater fitness in stationary phase evolved and rapidly took over the cultures. [16] [17] [44] The Zambrano et al. paper in 1993 which published this finding was one of the earliest examples of evolution occurring in the laboratory, or experimental evolution. [18]
In the 1990s, Kolter's group began to focus on the regulation and genetic components of surface-associated communities of bacteria called biofilms. Before then, biofilms had been discovered and were studied in the context of biofouling and in engineering solutions to prevent biofouling, [45] [46] [47] but the genetics of biofilm formation was unexplored and most microbiologists did not view biofilm formation as a physiological process of bacterial cells. [48] [49] [50] The lab went on to discover major regulatory systems underpinning biofilm development [51] [52] and characterized key materials within the extracellular matrix of biofilms using model species like Pseudomonasaeruginosa, [53] [54] [55] Escherichia coli , [56] Vibrio cholerae , [57] [58] and Bacillus subtilis. [59] [60] [61] [62] Microbial biofilms have since become a major field of microbiology, recognized as a predominant lifestyle of microbes in nature, with relevance to medicine and infections caused by pathogenic bacteria. [63] [64]
Another body of research stemmed from work on biofilms in the Kolter group in collaboration with the laboratory of Richard Losick: the discovery that subpopulations of different functional cell types develop within single-species biofilms of the bacterium Bacillus subtilis . Some cells were found to express genes for motility, others for sporulation, cannibalism, surfactant production or the secretion of extracellular matrix. [26] Some cell types were found localized in clusters in different physical locations and time points during biofilm development. [25] Another study from the group in 2015 showed that collective behaviors like group migration across a surface can emerge due to interactions between multiple cell types. [27]
Much of Kolter's most recent work focused on interactions between several species in mixed communities, as they typically exist in natural environments. This work has produced several influential studies of the emergent properties and social behaviors of microbes while interacting with other species.
Kolter is an advocate and participant in the communication of microbial science to early career microbiologists and non-scientific audiences. [7] His work in this area began during his term as Co-Director of the Harvard Microbial Sciences Initiative from 2003 to 2018. In this role, Kolter organized an annual public lecture in Cambridge, Massachusetts on topics of general relevance, such as microbial foods and drinks like cheese, sake and wine. [65] His work in science communication then intensified in the years leading up to his retirement and now as an Emeritus professor through invited lectures, writing and museum projects. [8] [66]
From 2014 through 2018, Kolter and Scott Chimileski spearheaded two public exhibitions at the Harvard Museum of Natural History. [7] [11] World in a Drop: Photographic Explorations of Microbial Life was an artistic exhibition that featured imagery produced through Chimileski and Kolter's collaboration, and was open from August 2017 to January 2018. [67] Subsequently, Microbial Life: A Universe at the Edge of Sight opened in February 2018 as major special exhibition supported by the Alfred P. Sloan Foundation. Kolter and Chimileski are guest curators of Microbial Life and the exhibition remains open until March 2020. [10] These exhibitions have traveled internationally at the Eden Project in the UK and EAFIT University in Medellín, Colombia, among other locations. [7] [8] [68] [69] [70]
Chimileski and Kolter were also advisors and contributed imagery for Invisible Worlds at the Eden Project, a permanent exhibition sponsored by the Welcome Trust. [71] Their still and time-lapse imagery was featured in the Bacterial World Exhibition at the Oxford University Museum of Natural History in 2018, and in the World Unseen: Intersections of Art and Science at the David J. Sencer CDC Museum in Atlanta, Georgia in 2019.
Kolter has a long record of teaching at Harvard University and at international summer courses. At Harvard he taught Biofilm Dynamics and he is currently developing a Massive Open Online Course with HarvardX on fermentation and microbial foods. [72] He is a regular instructor at the Microbial Diversity Course at the Marine Biological Laboratory in Woods Hole, Massachusetts, the EMBO-FEBES summer microbiology course in Spetses, Greece and the John Innes/Rudjer Bošković Summer School in Applied Molecular Microbiology in Dubrovnik, Croatia. [7] In 2000, he received the ASM International Professorship Award. [7]
Kolter has been the cover editor of the Journal of Bacteriology since 1999 and was previously on the Board of Reviewing Editors for Science, mBio, and eLife. [7] [73]
Bacterial growth is proliferation of bacterium into two daughter cells, in a process called binary fission. Providing no mutation event occurs, the resulting daughter cells are genetically identical to the original cell. Hence, bacterial growth occurs. Both daughter cells from the division do not necessarily survive. However, if the surviving number exceeds unity on average, the bacterial population undergoes exponential growth. The measurement of an exponential bacterial growth curve in batch culture was traditionally a part of the training of all microbiologists; the basic means requires bacterial enumeration by direct and individual, direct and bulk (biomass), indirect and individual, or indirect and bulk methods. Models reconcile theory with the measurements.
A biofilm is a 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 a 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 process of cell-to-cell communication that allows bacteria to detect and respond to cell population density by gene regulation, typically as a means of acclimating to environmental disadvantages.
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus Bacillus, B. subtilis is rod-shaped, and can form a tough, protective endospore, allowing it to tolerate extreme environmental conditions. B. subtilis has historically been classified as an obligate aerobe, though evidence exists that it is a facultative anaerobe. B. subtilis is considered the best studied Gram-positive bacterium and a model organism to study bacterial chromosome replication and cell differentiation. It is one of the bacterial champions in secreted enzyme production and used on an industrial scale by biotechnology companies.
Bacteria are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit the air, soil, water, acidic hot springs, radioactive waste, and the deep biosphere of Earth's crust. Bacteria play a vital role in many stages of the nutrient cycle by recycling nutrients and the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of dead bodies; bacteria are responsible for the putrefaction stage in this process. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Bacteria also live in mutualistic, commensal and parasitic relationships with plants and animals. Most bacteria have not been characterised and there are many species that cannot be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.
The gene rpoF encodes the sigma factor sigma-28, a protein in Escherichia coli and other species of bacteria. Depending on the bacterial species, this gene may be referred to as sigD or fliA. The protein encoded by this gene has been found to be necessary for flagellum formation.
Swarming motility is a rapid and coordinated translocation of a bacterial population across solid or semi-solid surfaces, and is an example of bacterial multicellularity and swarm behaviour. Swarming motility was first reported by Jorgen Henrichsen and has been mostly studied in genus Serratia, Salmonella, Aeromonas, Bacillus, Yersinia, Pseudomonas, Proteus, Vibrio and Escherichia.
Shewanella oneidensis is a bacterium notable for its ability to reduce metal ions and live in environments with or without oxygen. This proteobacterium was first isolated from Lake Oneida, NY in 1988, hence its name.
A prokaryote is a single-cell organism whose cell lacks a nucleus and other membrane-bound organelles. The word prokaryote comes from the Ancient Greek πρό (pró), meaning 'before', and κάρυον (káruon), meaning 'nut' or 'kernel'. In the two-empire system arising from the work of Édouard Chatton, prokaryotes were classified within the empire Prokaryota. However in the three-domain system, based upon molecular analysis, prokaryotes are divided into two domains: Bacteria and Archaea. Organisms with nuclei are placed in a third domain: Eukaryota.
Persister cells are subpopulations of cells that resist treatment, and become antimicrobial tolerant by changing to a state of dormancy or quiescence. Persister cells in their dormancy do not divide. The tolerance shown in persister cells differs from antimicrobial resistance in that the tolerance is not inherited and is reversible. When treatment has stopped the state of dormancy can be reversed and the cells can reactivate and multiply. Most persister cells are bacterial, and there are also fungal persister cells, yeast persister cells, and cancer persister cells that show tolerance for cancer drugs.
Bacillus mojavensis is a bacterium. Bacillus axarquiensis and Bacillus malacitensis are considered later heterotypic synonyms of B. mojavensis. It is named after the Mojave Desert.
Bacillus vallismortis is a species of bacteria, with type strain DV1-F-3.
Everett Peter Greenberg 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. He is best known for his research on quorum sensing, and has received multiple awards for his work.
CsgD is a transcription and response regulator protein referenced to as the master modulator of bacterial biofilm development. In E. coli cells, CsgD is tasked with aiding the transition from planktonic cell motility to the stationary phase of biofilm formation, in response to environmental growth factors. A transcription analysis assay illustrated a heightened decrease in CsgD's DNA-binding capacity when phosphorylated at A.A. D59 of the protein's primary sequence. Therefore, in the protein's active form (unphosphorylated), CsgD is capable of carrying out its normal functions of regulating curli proteins (fimbria) and producing ECM polysaccharides (cellulose). Following a promoter-lacZ fusion assay of CsgD binding to specific target sites on E. coli's genome, two classes of binding targets were identified: group I genes and group II genes. The group I genes, akin to fliE and yhbT, exhibit repressed transcription following their interaction with CsgD, whilst group II genes, including yccT and adrA, illustrated active functionality. Other group I operons that illustrate repressed transcription include fliE and fliEFGH, for motile flagellum formation. Other group II genes, imperative to the transition towards stationary biofilm development, include csgBA, encoding for curli fimbriae, and adrA, encoding for the synthesis of cyclic diguanylate. In this context, c-di-GMP functions as a bacterial secondary messenger, enhancing the production of extracellular cellulose and impeding flagellum production and rotation.
Karen Visick is an American microbiologist and expert in bacterial genetics known for her work on the role of bacteria to form biofilm communities during animal colonization. She conducted doctoral research with geneticist Kelly Hughes at the University of Washington, where she identified a key regulatory checkpoint during construction of the bacterial flagellum. She conducted postdoctoral research on development of the Vibrio fischeri-Euprymna scolopes symbiosis with Ned Ruby at University of Southern California and University of Hawaiʻi. The bacteria are bioluminescent and provide light to the host. Visick and Ruby revealed that bacteria that do not produce light exhibit a defect during host colonization.
The Phosphate (Pho) regulon is a regulatory mechanism used for the conservation and management of inorganic phosphate within the cell. It was first discovered in Escherichia coli as an operating system for the bacterial strain, and was later identified in other species. The Pho system is composed of various components including extracellular enzymes and transporters that are capable of phosphate assimilation in addition to extracting inorganic phosphate from organic sources. This is an essential process since phosphate plays an important role in cellular membranes, genetic expression, and metabolism within the cell. Under low nutrient availability, the Pho regulon helps the cell survive and thrive despite a depletion of phosphate within the environment. When this occurs, phosphate starvation-inducible (psi) genes activate other proteins that aid in the transport of inorganic phosphate.
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.
Gemma Reguera is a Spanish-American microbiologist and professor at Michigan State University. She is the editor-in-chief of the journal Applied and Environmental Microbiology and was elected fellow of the American Academy of Microbiology in 2019. She is the recipient of the 2022 Alice C. Evans Award for Advancement of Women from the American Society for Microbiology. Her lab's research is focused on electrical properties of metal-reducing microorganisms.
Diffusible signal factor (DSF) is found in several gram-negative bacteria and play a role in the formation of biofilms, motility, virulence, and antibiotic resistance. Xanthomonas campestris was the first bacteria known to have DSF. The synthesis of the DSF can be seen in rpfF and rpfB enzymes. An understanding of the DSF signaling mechanism could lead to further disease control.