《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_P26-P30

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Amino acid chemistry 15 • • describes how the subunits pack together to create the overall structure of the protein. Even small changes in the primary structure of a protein may have a large effect on that protein’s properties. Even a single misplaced amino acid can alter the protein’s function. This situation occurs in certain genetic diseases such as sicklecell anemia. In that disease, a single glutamic acid molecule has been replaced by a valine molecule in one of the chains of the hemoglobin molecule, the protein that carries oxygen in red blood cells and gives them their characteristic color. This seemingly small error causes the hemoglobin molecule to be misshapen and the red blood cells to be deformed. Such red blood cells cannot distribute oxygen properly, do not live as long as normal blood cells, and may cause blockages in small blood vessels. Enzymes are large protein molecules that catalyze a broad spectrum of biochemical reactions. If even one amino acid in the enzyme is changed, the enzyme may lose its catalytic activity. The amino acid sequence in a particular protein is determined by the protein’s genetic code. The genetic code resides in specific lengths (called genes) of the polymer doxyribonucleic acid (DNA), which is made up of from 3000 to several million nucleotide units, including the nitrogeneous bases: adenine, guanine, cytosine, and thymine. Although there are only four nitrogenous bases in DNA, the order in which they appear transmits a great deal of information. Starting at one end of the gene, the genetic code is read three nucleotides at a time. Each triplet set of nucleotides corresponds to a specific amino acid. Occasionally there an error, or mutation, may occur in the genetic code. This mutation may correspond to the substitution of one nucleotide for another or to the deletion of a nucleotide. In the case of a substitution, the result may be that the wrong amino acid is used to build the protein. Such a mistake, as demonstrated by sickle cell anemia, may have grave consequences. In the case of a deletion, the protein may be lose its functionality or may be completely missing. The twenty most common amino acids. Illustrations reprinted by permission of Robert L. Wolke. womi_A 5/6/03 1:06 PM Page 15

Anaerobes and anaerobic infections WORLD OF MICROBIOLOGY AND IMMUNOLOGY 16 • • Amino acids are also the core construction materials for neurotransmitters and hormones. Neurotransmitters are chemicals that allow nerve cells to communicate with one another and to convey information through the nervous system. Hormones also serve a communication purpose. These chemicals are produced by glands and trigger metabolic processes throughout the body. Plants also produce hormones. Important neurotransmitters that are created from amino acids include serotonin and gamma-aminobutyric acid. Serotonin(C10H12N2O) is manufactured from tryptophan, and gamma-aminobutyric acid (H2N(CH2)3COOH) is made from glutamic acid. Hormones that require amino acids for starting materials include thyroxine (the hormone produced by the thyroid gland), and auxin (a hormone produced by plants). Thyroxine is made from tyrosine, and auxin is constructed from tryptophan. A class of chemicals important for both neurotransmitter and hormone construction are the catecholamines. The amino acids tyrosine and phenylalanine are the building materials for catecholamines, which are used as source material for both neurotransmitters and for hormones. Amino acids also play a central role in the immune system. Allergic reactions involve the release of histamine, a chemical that triggers inflammation and swelling. Histamine is a close chemical cousin to the amino acid histidine, from which it is manufactured. Melatonin, the chemical that helps regulate sleep cycles, and melanin, the one that determines the color of the skin, are both based on amino acids. Although the names are similar, the activities and component parts of these compounds are quite different. Melatonin uses tryptophan as its main building block, and melanin is formed from tyrosine. An individual’s melanin production depends both on genetic and environmental factors. Proteins in the diet contain amino acids that are used within the body to construct new proteins. Although the body also has the ability to manufacture certain amino acids, other amino acids cannot be manufactured in the body and must be gained through diet. Such amino acids are called the essential dietary amino acids, and include arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Foods such as meat, fish, and poultry contain all of the essential dietary amino acids. Foods such as fruits, vegetables, grains, and beans contain protein, but they may lack one or more of the essential dietary amino acids. However, they do not all lack the same essential dietary amino acid. For example, corn lacks lysine and tryptophan, but these amino acids can be found in soy beans. Therefore, vegetarians can meet their dietary needs for amino acids as long by eating a variety of foods. Amino acids are not stockpiled in the body, so it is necessary to obtain a constant supply through diet. A well-balanced diet delivers more protein than most people need. In fact, amino acid and protein supplements are unnecessary for most people, including athletes and other very active individuals. If more amino acids are consumed than the body needs, they will be converted to fat or metabolized and excreted in the urine. However, it is vital that all essential amino acids be present in the diet if an organism is to remain healthy. Nearly all proteins in the body require all of the essential amino acids in their synthesis. If even one amino acid is missing, the protein cannot be constructed. In cases in which there is an ongoing deficiency of one or more essential amino acids, an individual may develop a condition known as kwashiorkor, which is characterized by severe weight loss, stunted growth, and swelling in the body’s tissues. The situation is made even more grave because the intestines lose their ability to extract nutrients from whatever food is consumed. Children are more strongly affected by kwashiorkor than adults because they are still growing and their protein requirements are higher. Kwashiorkor often accompanies conditions of famine and starvation. See also Bacterial growth and division; Biochemistry; Cell cycle (eukaryotic), genetic regulation of; Cell cycle (prokaryotic), genetic regulation of; Cell cycle and cell division; Chromosomes, eukaryotic; Chromosomes, prokaryotic; DNA (Deoxyribonucleic acid); Enzymes; Genetic regulation of eukaryotic cells; Genetic regulation of prokaryotic cells; Genotype and phenotype; Molecular biology and molecular genetics AMINOGLYCOSIDE ANTIBIOTICS • see ANTIBIOTICS AMYLOID PLAQUES • see BSE AND CJD DISEASE ANAEROBES AND ANAEROBIC Anaerobes and anaerobic infections INFECTIONS Anaerobes are bacteria that are either capable of growing in the absence of oxygen (referred to as facultative anaerobes) or that absolutely require the absence of oxygen (these are also called obligate anaerobes). Among the oxygen-free environments in which such bacteria can grow are deep wounds and tissues in the body. Growth in these niches can produce infections. Examples of infections are gas gangrene (which is caused by Streptococcus pyogenes) and botulism (which is caused by Clostridium botulinum). Other anaerobic bacteria that are frequently the cause of clinical infections are members of the genus Peptostreptococcus and Bacteroides fragilis. There are a number of different types of anaerobic bacteria. Two fundamental means of differentiation of these types is by their reaction to the Gram stain and by their shape. The genus Clostridium consists of Gram-positive rod-shaped bacteria that form spores. Gram-positive rods that do not form spores include the genera Actinomyces, Bifidobacterium, Eubacterium, Propionibacterium, and Lactobacillus. Grampositive bacteria that are spherical in shape includes the genwomi_A 5/6/03 1:06 PM Page 16

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Anaphylaxis 17 • • era Peptostreptococcus, Streptococcus, and Staphylococcus. Rod-shaped bacteria that stain Gram-negative include Bacteroides, Campylobacter, and Fusobacterium. Finally, Gram-negative spherical bacteria are represented by the genus Veillonella. The word anaerobic means “life without air.” In the human body, regions that can be devoid of oxygen include the interior of dental plaque that grows on the surface of teeth and gums, the gastrointestinal tract, and even on the surface of the skin. Normally the anaerobic bacteria growing in these environments are benign and can even contribute to the body’s operation. Most of the bacteria in the body are anaerobes. However, if access to underlying tissues is provided due to injury or surgery, the bacteria can invade the new territory and establish an infection. Such bacteria are described as being opportunistic pathogens. That is, given the opportunity and the appropriate conditions, they are capable of causing an infection. Typically, anaerobic bacteria cause from five to ten per cent of all clinical infections. Anaerobic infections tend to have several features in common. The infection is usually accompanied by a foulsmelling gas or pus. The infections tend to be located close to membranes, particularly mucosal membranes, as the infection typically begins by the invasion of a region that is bounded by a membrane. Anaerobic infections tend to involve the destruction of tissue, either because of bacterial digestion or because of destructive enzymes that are elaborated by the bacteria. This type of tissue damage is known as tissue necrosis. The tissue damage also frequently includes the production of gas or a fluid. There are several sites in the body that are prone to infection by anaerobic bacteria. Infections in the abdomen can produce the inflammation of the appendix that is known as appendicitis. Lung infections can result in pneumonia, infection of the lining of the lung (empyema) or constriction of the small air tubes known as bronchi (bronchiectasis). In females, pelvic infections can inflame the lining of the uterus (endometritis). Mouth infections can involve the root canals or gums (gingivitis). Infections of the central nervous system can lead to brain and spinal cord infections. Infection of the skin, via bites and other routes of entry, causes open sores on the skin and tissue destruction. An example is that massive and potentially lethal tissue degradation, which is known as necrotizing fascitis, and which is caused by group A b-hemolytic Streptococcus. Finally, infection of the bloodstream (bacteremia) can prelude the infection of the heart (endocarditis). The diagnosis of anaerobic infections is usually based on the symptoms, site of the infection and, if the infection is visible, on both the appearance and smell of the infected area. Most of the bacteria responsible for infection are susceptible to one or more antibiotics. Treatment can be prolonged, however, since the bacteria are often growing slowly and since antibiotics rely on bacterial growth to exert their lethal effect. In the case of infections that create tissue destruction, the removal of the affected tissue is an option to prevent the spread of the infection. Amputation of limbs is a frequent means of dealing with necrotizing fascitis, an infection that is inside of tissue (and so protected from antibiotics and the host’s immune response) and is exceptional in that it can swiftly spread. See also Bacteria and bacterial infections ANAPHYLACTIC SHOCK • see IMMUNITY: ACTIVE, PASSIVE, AND DELAYED AAnaphylaxisNAPHYLAXIS Anaphylaxis is a severe allergic reaction. The symptoms appear rapidly and can be life threatening. The symptoms of anaphylaxis include the increased output of fluid from mucous membranes (e.g., passages lining the nose, mouth, and throat), skin rash (e.g., hives), itching of the eyes, gastrointestinal cramping, and stiffening of the muscles lining the throat and trachea. As a result of the latter, breathing can become difficult. These symptoms do not appear in every case. However, some sort of skin reaction is nearly always evident. Anaphylaxis results from the exposure to an antigen with which the individual has had previous contact, and has developed a heightened sensitivity to the antigen. Such an antigen is also known as an allergen. The allergen binds to the specific immune cell (e.g., immunoglobulin E, also known as IgE) that was formed in response to the initial antigen exposure. IgE is also associated with other specific cells of the immune system that are called basophils and mast cells. The basophils and mast cells react to the binding of the allergenIgE complex by releasing compounds that are known as mediators (e.g, histamine, prostaglandin D2, trypase). Release of mediators does not occur when IgE alone binds to the basophils or mast cells. The release of the mediators triggers the physiological reactions. For example, blood vessels dilate (become larger in diameter) and fluid can pass across the blood vessel wall more easily. Because the immune system is sensitized to the particular allergen, and because of the potent effect of mediators, the development of symptoms can be sudden and severe. A condition called anaphylactic shock can ensue, in which the body’s physiology is so altered that failure of functions such as the circulatory system and breathing can occur. For example, in those who are susceptible, a bee sting, administration of a penicillin-type of antibiotic, or the ingestion of peanuts can trigger symptoms that can be fatal if not addressed immediately. Those who are allergic to bee stings often carry medication with them on hikes. Anaphylaxis occurs with equal frequency in males and females. No racial predisposition towards anaphylaxis is known. The exact number of cases is unknown, because many cases of anaphylaxis are mistaken for other conditions (e.g., food poisoning). However, at least 100 people die annually in the United States from anaphylactic shock. See also Allergies; Immunoglobulins and immunoglobulin deficiency syndromes womi_A 5/6/03 1:06 PM Page 17

Animal models of infection WORLD OF MICROBIOLOGY AND IMMUNOLOGY 18 • • AAnimal models of infection NIMAL MODELS OF INFECTION The use of various animals as models for microbiological infections has been a fundamental part of infectious disease research for more than a century. Now, techniques of genetic alteration and manipulation have made possible the design of animals so as to be specifically applicable to the study of a myriad of diseases. The intent for the use of animals as models of disease is to establish an infection that mimics that seen in the species of concern, usually humans. By duplicating the infection, the reasons for the establishment of the infection can be researched. Ultimately, the goal is to seek means by which the infection can be thwarted. Development of a vaccine to the particular infection is an example of the successful use of animals in infectious disease research. The development of the idea that maladies could be caused by bacterial infection grow from animals studies by Louis Pasteur in the mid-nineteenth century. The use of animals as models of cholera and anthrax enabled Pasteur to develop vaccines against these diseases. Such work would not have been possible without the use of animals. Subsequent to Pasteur, the use of animal models for a myriad of bacterial and viral diseases has led to the production of vaccines to diseases such as diphtheria, rabies, tuberculosis, poliomyelitis, measles, and rubella. Animal models are also used to screen candidate drugs for their performance in eliminating the infection of concern and also to evaluate adverse effects of the drugs. While some of this work may be amenable to study using cells grown on in the laboratory, and by the use of sophisticated computer models that can make predictions about the effect of a treatment, most scientists argue that the bulk of drug evaluation still requires a living subject. A key to developing an animal model is the selection of an animal whose physiology, reaction to an infection, and the nature of the infection itself all mirror as closely as possible the situation in humans. The study of an infection that bears no resemblance to that found in a human would be fruitless, in terms of developing treatment strategies for the human condition. Drawing depicting Louis Pasteur (right) using an animal model. womi_A 5/6/03 1:06 PM Page 18

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Anthrax 19 • • The need to mirror the human situation has led to the development of animal models that are specifically tailored for certain diseases. One example is the so-called nude mouse, which derives its name from the fact that it has no hair. Nude mice lack a thymus, and so are immunodeficient in a number of ways. Use of nude mice has been very useful in the study of immunodeficiency diseases in humans, such as acquired immunodeficiency syndrome. As well, this animal model lends itself to the study of opportunistic bacterial infections, which typically occur in humans whose immune systems are compromised. Depending on the infection and the focus of study, other animals have proven to be useful in infectious disease research. These animals include the rabbit, rat, guinea pig, pig, dog, and monkey. The latter in particular has been utilized in the study of AIDS, as primates are the genetically closest relatives to humans. The advent of molecular techniques of genetic alteration has made the development of genetically tailored animal models possible. Thus, for example, mouse models exist in which the activity of certain genes has been curtailed. These are known as transgenic animals. The involvement of the gene product in the infectious process is possible on a scale not possible without the use of the animal. The data from animal models provides a means of indicating the potential of a treatment. Furthermore, if a disease in an animal does not exactly mimic the human’s condition, for example cystic fibrosis in mice, the use of the animal model provides a guide towards establishing the optimal treatment in humans. In other words, the animal model can help screen and eliminate the undesirable treatments, narrowing the successful candidates for use in human studies. Further study, involving humans, is always necessary before something such as a vaccine can be introduced for general use. Such human studies are subject to rigorous control. The use of animals in research has long been a contentious issue, mainly due to questions of ethical treatment. This climate has spawned much legislation concerning the treatment of research animals. As well, in most institutions, an evaluation committee must approve the use of animals. If the research can be accomplished in some other way than through the use of living animals, then approval for the animal study is typically denied. See also AIDS, recent advances in research and treatment; Giardia and giardiasis; Immunodeficiency ANIMALCULES • see HISTORY OF MICROBIOLOGY AAnthrax NTHRAX Anthrax refers to a pulmonary disease that is caused by the bacterium Bacillus anthracis. This disease has been present since antiquity. It may be the sooty “morain” in the Book of Exodus, and is probably the “burning wind of plague” that begins Homer’s Iliad. Accounts by the Huns during their sweep across Eurasia in 80 A.D. describe mass deaths among their horse and cattle attributed to anthrax. These animals, along with sheep, are the primary targets of anthrax. Indeed, loss to European livestock in the eighteenth and nineteenth centuries stimulated the search for a cure. In 1876, Robert Koch identified the causative agent of anthrax. The use of anthrax as a weapon is not a new phenomenon. In ancient times, diseased bodies were used to poison wells, and were catapulted into cities under siege. In modern times, research into the use of anthrax as a weapon was carried out during World Wars I and II. In World War II, Japanese and German prisoners were subjects of medical research, including their susceptibility to anthrax. Allied efforts in Canada, the U.S. and Britain to develop anthrax-based weapons were also active. Britain actually produced five million anthrax cakes at the Porton Down facility, to be dropped on Germany to infect the food chain. In non-deliberate settings, humans acquire anthrax from exposure to the natural reservoirs of the microorganism; livestock such as sheep or cattle or wild animals. Anthrax has been acquired by workers engaged in shearing sheep, for example. Human anthrax can occur in three major forms. Cutaneous anthrax refers to the entry of the organism through a cut in the skin. Gastrointestinal anthrax occurs when the organism is ingested in food or water. Finally, inhalation anthrax occurs when the organism is inhaled. All three forms of the infection are serious, even lethal, if not treated. With prompt treatment, the cutaneous form is often cured. Gastrointestinal anthrax, however, can still be lethal in 25–75% of people who contract it. Inhalation anthrax is almost always fatal. The inhalation form of anthrax can occur because of the changing state of the organism. Bacillus anthracis can live as a large “vegetative” cell, which undergoes cycles of growth and division. Or, the bacterium can wait out the nutritionally bad times by forming a spore and becoming dormant. The spore is designed to protect the genetic material of the bacterium during hibernation. When conditions are conducive for growth and reproduction the spore resuscitates and active life goes on again. The spore form can be easily inhaled. Only 8,000 spores, hardly enough to cover a snowflake, are sufficient to cause the pulmonary disease when they resuscitate in the warm and humid conditions deep within the lung. The dangers of an airborne release of anthrax spores is well known. British open-air testing of anthrax weapons in 1941 on Gruinard Island in Scotland rendered the island uninhabitable for five decades. In 1979, an accidental release of a minute quantity of anthrax spores occurred at a bioweapons facility near the Russian city of Sverdlovsk. At least 77 people were sickened and 66 died. All the affected were some four kilometers downwind of the facility. Sheep and cattle up to 50 kilometers downwind became ill. Three components of Bacillus anthracis are the cause of anthrax. First, the bacterium can form a capsule around itself. The capsule helps shield the bacterium from being recognized by the body’s immune system as an invader, and helps fend off antibodies and immune cells that do try to deal womi_A 5/6/03 1:06 PM Page 19