Virginia Miller | |
|---|---|
 At the 2022 Microbe annual meeting | |
| Alma mater | |
| Scientific career | |
| Institutions | |
| Thesis | Analysis of the cholera toxin positive regulatory gene, toxR (1985) |
Virginia L. Miller is a microbiologist known for her work on studying the factors leading to disease caused by bacteria. Miller is an elected fellow of the American Academy of Microbiology (2003) and a former Pew Charitable Trust Biomedical Scholar (1989). [1]
Miller has a B.A. from the University of California, Santa Barbara (1979). [2] She earned her Ph.D. from Harvard University in 1985 where she worked on the expression of genes associated with Cholera toxin. [3] Following her Ph.D., she was a postdoc at Stanford University. [4] She moved to the University of California, Los Angeles in 1988 and earned tenure in 1994. [5] She moved to Washington University in St. Louis in 1996, and then to the University of North Carolina at Chapel Hill in 2008. [4] As of 2021, Miller is a professor of genetics, microbiology, and immunology at the University of North Carolina at Chapel Hill. [2]
Miller is known for her research into bacterial pathogenesis, the factors leading to the onset of disease from specific species of bacteria. [6] [7] [8] [9] [10] Her early research examined the synthesis of the cholera toxin by Vibrio cholerae [11] [12] and identified environmental signals that lead V. cholerae to express the proteins needed to make the cholera toxin. [13] She went on to examine the mechanisms by which another bacteria pathogen - Yersinia pestis - enters cells [14] and cause disease. [15] She has also worked on how Salmonella [16] [17] and Klebsiella pneumoniae [18] [19] cause disease. In brief, she mostly worked in the areas of Microbiology, Yersinia enterocolitica and Virulence. [20]
In 1989, Miller was named a Pew Scholar. [1] In 2003, Miller was elected a fellow of the American Academy of Microbiology. [21] [5]
Yersinia pestis is a gram-negative, non-motile, coccobacillus bacterium without spores that is related to both Yersinia enterocolitica and Yersinia pseudotuberculosis, the pathogen from which Y. pestis evolved and responsible for the Far East scarlet-like fever. It is a facultative anaerobic organism that can infect humans via the Oriental rat flea. It causes the disease plague, which caused the Plague of Justinian and the Black Death, the deadliest pandemic in recorded history. Plague takes three main forms: pneumonic, septicemic, and bubonic. Yersinia pestis is a parasite of its host, the rat flea, which is also a parasite of rats, hence Y. pestis is a hyperparasite.
Vibrio cholerae is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimp, and other shellfish. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease called cholera, which can be derived from the consumption of undercooked or raw marine life species or drinking contaminated water.
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.
Vibrio vulnificus is a species of Gram-negative, motile, curved rod-shaped (vibrio), pathogenic bacteria of the genus Vibrio. Present in marine environments such as estuaries, brackish ponds, or coastal areas, V. vulnificus is related to V. cholerae, the causative agent of cholera. At least one strain of V. vulnificus is bioluminescent. Increasing seasonal ocean temperatures and low-salt marine environments like estuaries favor a greater concentration of Vibrio within filter-feeding shellfish; V. vulnificus infections in the Eastern United States have increased eightfold from 1988–2018.
Yersinia enterocolitica is a Gram-negative, rod-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29°C (72–84°F), but becomes nonmotile at normal human body temperature. Y. enterocolitica infection causes the disease yersiniosis, which is an animal-borne disease occurring in humans, as well as in a wide array of animals such as cattle, deer, pigs, and birds. Many of these animals recover from the disease and become carriers; these are potential sources of contagion despite showing no signs of disease. The bacterium infects the host by sticking to its cells using trimeric autotransporter adhesins.
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. Several different serogroups of Shigella are described; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics, although some strains have become resistant. Less severe cases are not usually treated because they become more resistant in the future. Shigella are closely related to Escherichia coli, but can be differentiated from E.coli based on pathogenicity, physiology and serology.
Yersinia pseudotuberculosis is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by Y. pseudotuberculosis. The bacterium is urease positive.
Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:
The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining five components are B subunits. All of these toxins share a similar structure and mechanism for entering targeted host cells. The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions.
Virulence-related outer membrane proteins, or outer surface proteins (Osp) in some contexts, are expressed in the outer membrane of gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion.
Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.
The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.
The CTXφ bacteriophage is a filamentous bacteriophage. It is a positive-strand DNA virus with single-stranded DNA (ssDNA).
The alpha-D-phosphohexomutases are a large superfamily of enzymes, with members in all three domains of life. Enzymes from this superfamily are ubiquitous in organisms from E. coli to humans, and catalyze a phosphoryl transfer reaction on a phosphosugar substrate. Four well studied subgroups in the superfamily are:
Yersinia bercovieri is a Gram-negative species of enteric bacteria.
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.
Virstatin is a small molecule that inhibits the activity of the cholera protein, ToxT.
Daniel A. Portnoy is a microbiologist, the Edward E. Penhoet Distinguished Chair in Global Public Health and Infectious Diseases, and a professor of biochemistry, Biophysics and Structural Biology in the Department of Molecular and Cell Biology and in the Division of Microbiology in the Department of Plant and Microbial Biology at the University of California, Berkeley. He is one of the world's foremost experts on Listeria monocytogenes, the bacterium that causes the severe foodborne illness Listeriosis. He has made seminal contributions to multiple aspects of bacterial pathogenesis, cell biology, innate immunity, and cell mediated immunity using L. monocytogenes as a model system and has helped to push forward the use of attenuated L. monocytogenes as an immunotherapeutic tool in the treatment of cancer.
John Mekalanos is a microbiologist who is primarily known for leading one of the first teams that reported the discovery of the type VI secretion system as well as his work on the pathogenicity of the bacterial species Vibrio cholerae, its toxin, and its secretion systems. Since 1998, he has been a member of the National Academy of Sciences.
Theresa Marie Koehler is an American microbiologist who is the Herbert L. and Margaret W. DuPont Distinguished Professor in Biomedical Sciences and Chair of the Department of Microbiology and Molecular Genetics at McGovern Medical School. She is known for her extensive research on anthrax and was elected Fellow of the American Association for the Advancement of Science in 2021.