《微生物生物学》课程教学资源（书籍文献）World of Microbiology and Immunology，Brigham Narins, Editor，Volumes 1 and 2 A-Z.pdf_P21-P25

Alexander, Hattie Elizabeth WORLD OF MICROBIOLOGY AND IMMUNOLOGY 10 • • ity that vaccination would create “carriers,” individuals who are not sick but who are capable of spreading the disease. There are various vaccine treatment strategies. One involves the injection of so-called “naked” DNA. The DNA contains genes that code for gag, a viral component thought to be critical to the development of AIDS. The DNA can be attached to inert particles that stimulate the response of the immune system. In another strategy, the viral gene is bundled into the DNA of another virus that is injected into the patient. As of 2002, more than two dozen experimental vaccines intended to control, but not cure, AIDS infections are being studied worldwide. Treatment strategies, vaccine-based or otherwise, will need to address the different isolates of the AIDS virus that are present in various regions of the globe. These different isolates tend to be separated into different geographical regions. Even within a geographical area, an isolate can display variation from place to place. Thus, it has become clear that a universal treatment strategy is unlikely. See also Human immunodeficiency virus (HIV); Immune stimulation, as a vaccine; Vaccination ALEXANDER, HATTIE ELIZABETH (1901-1968) Alexander, Hattie Elizabeth American physician and microbiologist Hattie Elizabeth Alexander was a pediatrician and microbiologist who made fundamental contributions in the early studies of the genetic basis of bacterial antibiotic resistance, specifically the resistance displayed by Hemophilus influenzae, the cause of influenzal meningitis (swelling of the nerves in the spinal cord and brain). Her pioneering studies paved the way for advances in treatment that have saved countless lives. Alexander was born in Baltimore, Maryland. She received her B.A. degree from Goucher College in 1923. After working as a public health bacteriologist from 1923 to 1926, she entered the Johns Hopkins School of Medicine. She received her M.D. in 1930. Alexander assumed a residency at New York City Babies Hospital in 1930. She remained there for the remainder of her career, attaining the rank of Professor in 1957. Alexander pioneered studies of the antibiotic resistance and susceptibility of Hemophilus influenzae. In 1939 she successfully utilized an anti-pneumonia serum that had been developed at Rockefeller University to cure infants of influenzal meningitis. Until then, infection with Hemophilus influenzae type b almost always resulted in death. Her antiserum reduced the death rate by almost 80%. Further research led to the use of sulfa drugs and other antibiotics in the treatment of the meningitis. In other research, Alexander established that Hemophilus influenzae was the cause of a malady known as epiglottitis (also called croup). Her discovery prompted research that has led to effective treatments for croup. In the 1950s Alexander began studies on the genetic basis of antibiotic resistance. During the next two decades she made fundamental observations concerning bacterial and viral genetics. She demonstrated that the ability of Hemophilus influenzae to cause disease rested with its genetic material. Additionally she demonstrated that the genetic material of poliovirus could infect human cells. She also proposed that the mechanisms of inheritance of traits in microorganisms could be similar to the mechanisms operating in humans. Time has borne out her suggestion. In addition to her research, Alexander devoted much time to teaching and clinical duties. For her research and other professional accomplishments Alexander received many awards, honorary degrees, and other honors. Notably she became the first woman president of the American Pediatric Society in 1965. See also Bacterial adaptation; Microbial genetics ALGAE, ECONOMIC USES AND BENEFITS • see ECONOMIC USES AND BENEFITS OF MICROORGANISMS AAllergies LLERGIES An allergy is an excessive or hypersensitive response of the immune system to harmless substances in the environment. Instead of fighting off a disease-causing foreign substance, the immune system launches a complex series of actions against an irritating substance, referred to as an allergen. The immune response may be accompanied by a number of stressful symptoms, ranging from mild to severe to life threatening. In rare cases, an allergic reaction leads to anaphylactic shock—a condition characterized by a sudden drop in blood pressure, difficulty in breathing, skin irritation, collapse, and possible death. The immune system may produce several chemical agents that cause allergic reactions. Some of the main immune system substances responsible for the symptoms of allergy are the histamines that are produced after an exposure to an allergen. Along with other treatments and medicines, the use of antihistamines helps to relieve some of the symptoms of allergy by blocking out histamine receptor sites. The study of allergy medicine includes the identification of the different types of allergy, immunology, and the diagnosis and treatment of allergy. The most common causes of allergy are pollens that are responsible for seasonal or allergic rhinitis. The popular name for rhinitis, hay fever, a term used since the 1830s, is inaccurate because the condition is not caused by fever and its symptoms do not include fever. Throughout the world during every season, pollens from grasses, trees, and weeds produce allergic reactions like sneezing, runny nose, swollen nasal tissues, headaches, blocked sinuses, and watery, irritated eyes. Of the 46 million allergy sufferers in the United States, about 25 million have rhinitis. womi_A 5/6/03 1:06 PM Page 10

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Amebic dysentery 11 • • Dust and the house dust mite constitute another major cause of allergies. While the mite itself is too large to be inhaled, its feces are about the size of pollen grains and can lead to allergic rhinitis. Other types of allergy can be traced to the fur of animals and pets, food, drugs, insect bites, and skin contact with chemical substances or odors. In the United States, there are about 12 million people who are allergic to a variety of chemicals. In some cases an allergic reaction to an insect sting or a drug reaction can cause sudden death. Serious asthma attacks are sometimes associated with seasonal rhinitis and other allergies. About nine million people in the United States suffer from asthma. Some people are allergic to a wide range of allergens, while others are allergic to only a few or none. The reasons for these differences can be found in the makeup of an individual’s immune system. The immune system is the body’s defense against substances that it recognizes as dangerous to the body. Lymphocytes, a type of white blood cell, fight viruses, bacteria, and other antigens by producing antibodies. When an allergen first enters the body, the lymphocytes produce an antibody called immunoglobulin E (IgE). The IgE antibodies attach to mast cells, large cells that are found in connective tissue and contain histamines along with a number of other chemical substances. Studies show that allergy sufferers produce an excessive amount of IgE, indicating a hereditary factor for their allergic responses. How individuals adjust over time to allergens in their environments also determines their degree of susceptibility to allergic disorders. The second time any given allergen enters the body, it becomes attached to the newly formed Y-shaped IgE antibodies. These antibodies, in turn, stimulate the mast cells to discharge its histamines and other anti-allergen substances. There are two types of histamine: H1 and H2. H1 histamines travel to receptor sites located in the nasal passages, respiratory system, and skin, dilating smaller blood vessels and constricting airways. The H2 histamines, which constrict the larger blood vessels, travel to the receptor sites found in the salivary and tear glands and in the stomach’s mucosal lining. H2 histamines play a role in stimulating the release of stomach acid, thus contributing to a seasonal stomach ulcer condition. The simplest form of treatment is the avoidance of the allergic substance, but that is not always possible. In such cases, desensitization to the allergen is sometimes attempted by exposing the patient to slight amounts of the allergen at regular intervals. Antihistamines, which are now prescribed and sold over the counter as a rhinitis remedy, were discovered in the 1940s. There are a number of different antihistamines, and they either inhibit the production of histamine or block them at receptor sites. After the administration of antihistamines, IgE receptor sites on the mast cells are blocked, thereby preventing the release of the histamines that cause the allergic reactions. The allergens are still there, but the body’s “protective” actions are suspended for the period of time that the antihistamines are active. Antihistamines also constrict the smaller blood vessels and capillaries, thereby removing excess fluids. Recent research has identified specific receptor sites on the mast cells for the IgE. This knowledge makes it possible to develop medicines that will be more effective in reducing the symptoms of various allergies. Corticosteroids are sometimes prescribed to allergy sufferers as anti-inflammatories. Decongestants can also bring relief, but these can be used for a short time only, since their continued use can set up a rebound effect and intensify the allergic reaction. See also Antibody and antigen; Antibody-antigen, biochemical and molecular reactions; Antibody formation and kinetics; Antigenic mimicry; Immunology AAmebic dysentery MEBIC DYSENTERY Amebic (or amoebic) dysentery, which is also referred to as amebiasis or amoebiasis, is an inflammation of the intestine caused by the parasite Entamoeba histolytica. The severe form of the malady is characterized by the formation of localized lesions, called ulcers, in the intestine, especially in the region known as the colon, abscesses in the liver and the brain, and by vomiting, severe diarrhea with fluid loss leading to dehydration, and abdominal pain. Amebic dysentery is one of the two most common causes of intestinal inflammation worldwide. The other is infection with bacteria of the Shigella group. Amebiasis is contracted mainly by ingesting the parasite in contaminated food or water. Person–to–person transmission is less likely, but can occur. The disease is thus most common where sanitation is poor, in the developing world. The disease is especially prevalent in regions where untreated human waste is used as fertilizer. Run–off from fields can contaminate wells contaminating the drinking water. Amebiasis can occur anywhere in the world in almost any climate, excluding polar areas and mountainous high altitudes. Even now, approximately 500 cases are reported each year in New York State. Hayfever allergy triggered by oilseed rape plants. womi_A 5/6/03 1:06 PM Page 11

American Type Culture Collection WORLD OF MICROBIOLOGY AND IMMUNOLOGY 12 • • Those infected with the parasite may develop the severe symptoms listed above, a milder condition characterized by nausea, loose bowel movements and pain in the abdomen, or sometimes no symptoms at all. The latter is a concern to others, as the asymptomatic person can still pass the parasite in his/her feces and so potentially spread the infection to others. Indeed, such transmission can persist even years after exposure to the parasite. Entamoeba histolytica can occur in two forms. The parasite is excreted to the environment as a so-called cyst from. This form is very hardy, and is analogous to a bacterial spore. This form is designed for longevity, to preserve the genetic material of the parasite when in inhospitable environments. Once in a more favorable environment, such as the intestinal tract of humans, the cyst resuscitates and growth resumes. The active and growing form of the parasite is known as a trophozoite. It is the trophozoite that causes the symptoms of amebiasis. Some trophozoites will re-encyst and exit via the feces, to become a potential source of further infection. If the cyst stays in the intestinal tract after being ingested then they have little adverse effect. However, if the cysts invade the walls of the intestine, ulcers and diarrhea can be produced. Amebiasis can be fairly short in duration, lasting only a few weeks. Or, the infection may become chronic. The chronic form can be ominous, as the trophozoite can invade the blood and be carried all over the body. The abscesses formed in the liver and brain can be very destructive. Both amebiasis and the causative parasite have been known for a long time. The parasite was described in great detail and given its name in 1903. Despite this long history, the diagnosis of the malady still relies on the visual detection of the parasite in fecal material obtained from a suspected patient. Often fecal samples need to be examined for several days to detect the presence of cysts. Amebiasis is still easily misdiagnosed, especially when no symptoms are present. Also the parasite can be visually similar to harmless normal residents of the intestinal tract, such as Entamoeba coli, and can co-exist with bacteria that themselves are the cause of the symptoms being experienced by the infected person. Amebiasis is treatable, usually by a combination of drugs. An amebicide will kill the organisms in the intestinal tract, while an antibiotic will treat any bacteria that have been ingested with the feces, contaminated water, or food. Finally, if warranted, a drug can be administered to retard the spread of the infection to tissues such as the liver. See also Parasites AAmerican Type Culture Collection MERICAN TYPE CULTURE COLLECTION The American Type Culture Collection, which is also known as the ATCC, is a not-for-profit bioscience organization that maintains the world’s largest and most diverse collection of microbiological life. Many laboratories and institutions maintain their own stockpile of microorganisms, usually those that are in frequent use in the facility. Some large culture collections are housed and maintained, usually by universities or private enterprises. But none of these rivals the ATCC in terms of size. The ATCC collection includes repositories of bacterial species, animal viruses, cell lines (which are important for the growth of certain types of viruses), fungi, plant viruses, protists (microscopic organisms that have a nucleus that is contained within a membrane), and yeasts. As well, in conjunction with researchers at George Mason University, which borders the ATCC facility, research in areas such as bioinformatics is carried out. The ATCC was founded, and continues to function, to acquire, confirm the identity of, preserve and distribute biological materials to scientists worldwide. Since its inception, the mandate has expanded to now include information technology and intellectual property. Today, in addition to offering the microbiological organisms for sale, the ATCC offers technical services and educational programs to academic, government, and private organizations. The genesis of the ATCC began in 1921. Then, the Army Medical Museum accepted a then renowned culture collection called the Winslow Culture Collection. The collection was put under the care of the Washington, D.C. members of the Society of American Bacteriologists (in time, this society grew in scope and membership to become the American Society for Microbiology). In 1925, the ATCC became an official entity with its incorporation. The burgeoning culture collection was moved to the McCormick Institute in Chicago. Twelve years later the collection returned to Washington. Space was leased to house the collection. Over the years the increasing diversification of the ATCC and the acquisition of more cultures taxed the space, so a series of moves to larger and larger sites occurred. Finally, in 1998, the organization moved to the state-of-theart facility it continues to occupy. Technician at The American Type Culture Collection. womi_A 5/6/03 1:06 PM Page 12

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Ames, Bruce N. 13 • • The present facility is 106,000 square feet in size and has almost 35,000 square feet of laboratory space, including specialized containment facilities for more hazardous house microorganisms. Over fifty ultra-low temperature freezers are used for the long-term storage of samples. Such storage avoids changes in the organisms that could result from storage at refrigeration temperatures. See also Cryoprotection AAmes, Bruce N. MES, BRUCE N. (1928- ) American biochemist and molecular biologist Bruce N. Ames is a professor of biochemistry and molecular biology at the University of California at Berkeley. He is best known for the development of a test used as an indicator of the carcinogenicity (cancer-causing potential) of chemicals. Known as the Ames test, it measures the rate of mutation in bacteria after the introduction of a test substance. Ames’s research led to a greater appreciation of the role of genetic mutation in cancer and facilitated the testing of suspected cancer-causing chemicals. He also developed a database of chemicals that cause cancer in animals, listing their degree of virulence. Ames has been involved in numerous controversies involving scientific and environmental policies relevant to cancer prevention. In the 1970s he vociferously advocated strict government control of synthetic chemicals. In the 1980s, however, the discovery that many natural substances were also mutagenic (causing gene mutation), and thus possibly cancer causing, led him to reverse his original position. Ames was born in New York City, the son of Dr. Maurice U. and Dorothy Andres Ames. His father taught high school science and then became assistant superintendent of schools. Ames himself graduated from the Bronx High School of Science in 1946. He received a B.A. in biochemistry from Cornell University in 1950 and a Ph.D. in the same field from the California Institute of Technology in 1953. Ames worked at the National Institutes of Health, primarily in the National Institute of Arthritis and Metabolic Diseases, from 1953 to 1967. In 1968 he moved to the Department of Biochemistry and Molecular Biology at the University of California at Berkeley as a full professor. He was Chairman of the Department from 1984 to 1989. In addition he became Director of the National Institute of Environmental Health Science at the University in 1979. In the 1960s and early 1970s Ames developed a test that measured the degree to which synthetic chemicals cause gene mutation (a change in the deoxyribonucleic acid, or DNA, the molecule that carries genetic information). He began by deliberately mutating a Salmonella bacterium. The changed bacterium could not produce an amino acid called histidine that normal bacteria produce and that they need to survive. The next step was to add just enough histidine to allow the bacteria to live, and to add, as well, the synthetic chemical being tested. If the added chemical caused genetic mutation, the abnormal gene of the Salmonella bacteria would mutate and again be able to produce histidine. When this happened the added chemical was marked as a suspected carcinogen, because cancer is associated with somatic cell mutation (that is, mutation of any cells with the exception of germ cells). Over eighty percent of organic chemicals known to cause cancer in humans tested positive as mutagens in the test developed by Ames and his colleagues. This result gave support to the theory that somatic mutation causes cancer and helped to validate the use of the test for initial identification of mutagens when considering synthetic chemicals for industrial and commercial use. In addition to these practical results, the research of Ames and a colleague, H. J. Whitfield, Jr., led to important advances in understanding the biochemistry of mutagenesis. Beyond his work in genetic toxicology, Ames made important discoveries in molecular biology, including ground-breaking studies on the regulation of the histidine operon (the gene or locus of the gene that controls histidine) and the role of transfer ribonucleic acid (RNA) in that regulation. In the 1980s Ames set up a database of animal cancer test results with colleague Lois Swirsky Gold of Lawrence Berkeley Laboratory. The database is used to determine whether a chemical has tested positive as a carcinogen and gives the degree of its virulence. From these data Ames developed a value measuring the carcinogenic danger of a chemical to humans. HERP (daily Human Exposure dose/Rodent Potency dose) is the value determined by comparing the daily dose of a chemical that will cause cancer in half a group of test animals with the estimated daily dose to which humans are normally exposed. The result is a percentage that suggests the degree of carcinogenicity of a chemical for humans. In the 1970s Ames was a conspicuous advocate of particular regulatory and environmental public policies that relate to the cancer-causing potential of synthetic substances. In the 1970s Ames asserted that even trace amounts of mutagenic chemicals could cause a mutation (and thus possibly cancer). He found that tris (2,3-dibromopropyl) phosphate, the chemical that was used as a flame retardant on children’s pajamas, was a mutagen in the Ames test; he was instrumental in getting it banned. Similarly he found that some hair dyes contained mutagens. His advocacy led to governmental regulations that forced manufacturers to reformulate their products. In his position on the regulation of synthetic chemicals, he was a natural ally of environmentalists. However, in the early 1980s Ames reversed his position, arguing that there is no scientific evidence that small doses of most synthetic chemicals cause human cancers; he also argued that, in the absence of such evidence, they should not be controlled. This about-face was partly a result of a growing body of knowledge concerning the mutagenic properties of numerous chemicals found in nature. Ames began arguing against the existing large public expenditures for pollution control and the regulation of synthetic chemicals, noting that cancer might just as plausibly be caused by the chemicals in plants. His arguments were based primarily on three factors: his argument that more scientific evidence should be required before controls are implemented; his attitude toward the setting of priorwomi_A 5/6/03 1:06 PM Page 13

Amino acid chemistry WORLD OF MICROBIOLOGY AND IMMUNOLOGY 14 • • ities, which he argued should be centered on basic research rather than regulation; and finally his belief that the large public expenditures incurred by the regulatory process hurt American economic competitiveness. Ames and his colleague Gold have also argued that the use of bioassays (animal tests) of chemicals to predict their carcinogenic potential in humans should be abandoned. In a typical bioassay, rats are given a maximum tolerated dosage (MTD) of a particular chemical daily for a period of time (such as a year). The maximum tolerated dosage is as much as the animal can be given without immediately becoming ill or dying. At the end of the time period, the number of animals that have developed cancers is tabulated as an indicator of the cancer causing potential of the chemical being tested. Ames suggested that it is often the large dosage itself, rather than the nature of the particular chemical that induces the rat cancers. He argued that, since humans are not normally exposed to such large doses, the assays were not valid for predicting human cancers. Ames’s arguments have some support both within and outside scientific communities. However, he also has numerous critics. Those taking issue with his positions have noted that pollution control, for example, involves far more than just carcinogenicity. These critics suggest that Ames has not offered a substitute for animal assays (the Ames test has not proved to be such a substitute), and that neither he nor they have a good idea of what goes on at low dosages. Some argue that Ames has an over-simplified view of the regulatory process, which is based on a consideration of animal assays but also on other factors. It has also been argued that the discovery that many naturally occurring chemicals have a high mutagenic rate (just as synthetic chemicals) should not lead to the conclusion that synthetic chemicals pose less risk than was previously supposed. Such an assumption places too much emphasis on mutagenic rate as a sole indicator of carcinogenicity, ignoring the complex, multi-stage developmental process of the disease. Yet the disagreements between Ames and his critics are based on several points of commonality—that cancer is a complex multi-stage process that is not fully understood; that there is no perfect test or group of tests that can fully predict the potential carcinogenicity of many substances in humans; and that public regulatory and environmental policies must be made and carried out in spite of this deficiency of knowledge. As for Ames, he has described his public-policy activism as a hobby, and he has noted that his recent scientific work includes studies in the biochemistry of aging. Elected to the National Academy of Sciences in 1972, Ames has received many awards, including the Eli Lilly Award of the American Chemical Society (1964), the Mott Prize of the General Motors Cancer Research Foundation (1983), and the Gold Medal of the American Institute of Chemists (1991). He is the author or coauthor of more than 250 scientific articles. See also Chemical mutagenesis; Molecular biology and molecular genetics AAmino acid chemistry MINO ACID CHEMISTRY Amino acids are the building blocks of proteins and serve many other functions in living organisms. The prime function of DNA is to carry the information needed to direct the proper sequential insertion of amino acids into protein chain during protein synthesis (translation). An amino acid is a molecule that contains a terminal acidic carboxyl group (COOH) and a terminal basic amino group (NH2). The approximately 20 amino acids (plus a few derivatives) that have been identified as protein constituents are alpha-amino acids in which the -NH2 group is attached to the alpha-carbon next to the -COOH group. Thus, their basic structure is NH2CHRCOOH, where R is a side chain. This side chain, which uniquely characterizes each alpha-amino acid, determines the molecules overall size, shape, chemical reactivity, and charge. There are hundreds of alpha-amino acids, both natural and synthetic. The amino acids that receive the most attention are the alpha-amino acids that genes are codes for, and that are used to construct proteins. These amino acids include glycine NH2CH2COOH, alanine CH3CH (NH2) COOH, valine (CH3)2CHCH (NH2)COOH, leucine (CH3)2CHCH2CH(NH2) COOH, isoleucine CH3CH2CH(CH3)CH(NH2)COOH, methionine CH3SCH2CH2CH(NH2)COOH, phenylalanine C6H5CH2 CH(CH2)COOH, proline C4H8NCOOH, serine HOCH2CH (NH2)COOH, threonine CH3CH(OH)CH(NH2)COOH, cysteine HSCH2CH(NH2)COOH, asparagine, glutamine H2NC (O)(CH2)2CH(NH2)COOH, tyrosine C6H4OHCH2CHNH2 COOH, tryptophan C8H6NCH2CHNH2COOH, aspartate COOHCH2CH(NH2)COOH, glutamate COOH(CH2)2CH (NH2)COOH, histidine HOOCCH(NH2)CH2C3H3H2, lysine NH2(CH2)4CH(NH2)COOH, and arginine (NH2)C(NH) HNCH2CH2CH2CH(NH2)COOH. Proteins are one of the most common types of molecules in living matter. There are countless members of this class of molecules. They have many functions from composing cell structure to enabling cell-to-cell communication. One thing that all proteins have in common is that they are composed of amino acids. Proteins consist of long chains of amino acids connected by peptide linkages (-CO. NH-). A protein’s primary structure refers to the sequence of amino acids in the molecule. The protein’s secondary structure is the fixed arrangement of amino acids that results from interactions of amide linkages that are close to each other in the protein chain. The secondary structure is strongly influenced by the nature of the side chains, which tend to force the protein molecule into specific twists and kinks. Side chains also contribute to the protein’s tertiary structure, i.e., the way the protein chain is twisted and folded. The twists and folds in the protein chain result from the attractive forces between amino acid side chains that are widely separated from each other within the chain. Some proteins are composed of two of more chains of amino acids. In these cases, each chain is referred to as a subunit. The subunits can be structurally the same, but in many cases differ. The protein’s quaternary structure refers to the spatial arrangement of the subunits of the protein, and womi_A 5/6/03 1:06 PM Page 14