Science and Profession Microbiology is the field of science that focuses on microorganisms, or living things that can be studied only using microscopes and other special equipment. Microorganisms have an important place in the ecology of the planet. They form a basis for food chains and, as decomposers, recycle many materials in the environment. Because microbes are everywhere, humans come in contact with a wide variety every day; many live on or in the human body. Most of these organisms either are harmless or are prevented from multiplying by the body's immune system and other defenses. Others are able to penetrate these defenses and cause illness. Medical microbiologists study the microorganisms that cause these diseases. Such pathogens primarily fall into one of four groups: bacteria, fungi, protozoa, and viruses.
Bacteria, including cyanobacteria (often called blue-green algae, although they are not actually algae), were previously considered to belong to the Monera kingdom. Under the more recent three-domain system, which made kingdoms subgroups of domains, the organisms formerly in the Monera kingdom were divided between the domains Archaea and Bacteria (formerly Eubacteria). Bacteria are the simplest organisms that exist in cellular form; most have just one circular chromosome containing between several hundred and several thousand genes (compared to the more than twenty thousand protein-coding genes found in human DNA). Because it is unprotected by a nuclear membrane, bacterial DNA can be manipulated more easily than can DNA in plants and animals.
Several traits are used to identify bacterial species. There are three basic shapes: coccus (round), bacillus (rod), and spirillum (spiral). The gram staining procedure divides bacteria into two main groups based on their cell wall content. Other staining procedures can identify the presence of such structures as flagella, capsules, and endospores, which may have implications for control measures. For example, endospores are resistant to many common disinfectants, and boiling them for up to four hours may not destroy them. In addition to staining, chemical and metabolic tests are used to differentiate bacterial species.
Fungi belong to the domain Eukarya, kingdom Fungi. Although this kingdom includes larger organisms such as mushrooms, the ones of interest to medical microbiology are the yeasts, molds, and related microorganisms. Like plants, fungi have cell walls. However, they cannot manufacture their own food by photosynthesis and must either be saprophytes, living on dead organic material, or parasites, obtaining nutrients from another living organism. Fungi reproduce by means of spores that are released and carried by the air to a suitable medium. They thrive in a warm, moist environment with a carbohydrate source of food.
Protozoa, members of the Eukarya domain, Protista (or Protoctista) kingdom, are often referred to as one-celled animals. They have no cell walls and must ingest or absorb their food. Their ability to move enables them to spread more quickly than can nonmotile microbes. Protozoa have traditionally been divided into four main categories, based on their method of movement. Amoebas move by means of projections called pseudopodia; flagellates move by means of long hairlike structures (flagella) that whip back and forth; ciliates are covered with short hairlike structures (cilia) that beat in a synchronized manner to cause movement; and sporozoans must move by means of the circulation of blood and tissue fluids within a host. Of all the microorganisms, protozoa are the ones that most resemble human cells. Treatment for a protozoan disease must be monitored closely, as most chemicals that are effective against protozoa are also toxic to humans.
Viruses are on the borderline between living and nonliving things. They are not cellular in form, unlike all other forms of life. Each virus particle, called a virion, is made up of a protein coat and a nucleic acid core of either DNA or RNA. Viruses are classified by size, shape, type of nucleic acid in their core, and type of cell they invade or disease they cause.
To reproduce, a virion attaches itself to a living cell and injects its core into the cell. The nucleic acid then takes over the cell’s protein-manufacturing apparatus to make new virus particles. The host cell ruptures as these viruses are released to infect other cells. Some viral DNA can incorporate itself into the host DNA and remain dormant until some factor triggers a new reproductive cycle. Viruses usually can attack only one type of cell or species; however, mutations can occur that allow them to infect other species. For example, human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS), is believed to have mutated from simian immunodeficiency virus (SIV) in monkeys.
Diagnostic and Treatment Techniques When the type of microorganism causing an infectious disease is unknown, a medical microbiologist follows a series of procedures known as Koch’s postulates. Named for German bacteriologist Robert Koch, who first proposed them, these procedures identify and confirm that a particular microorganism is the cause of a disease. First, the microorganism must be present in the tissues of all individuals who have the disease. This means that all the microorganisms in a sample of diseased tissue must be identified and classified so that a possible pathogen may be differentiated from the normal flora. Second, the suspected pathogen must be isolated and grown in a pure culture. Many microorganisms can be grown on a simple medium called nutrient agar. Some microorganisms may need specific nutrients added to the medium, or they may be obligate parasites, meaning they can only grow on or in living cells. Anaerobic organisms cannot grow at all if oxygen is present. Since these special needs cannot be met if the identity of the organism is unknown, the detection of some pathogens in this manner may be difficult.
The third step the researcher takes is to inoculate an animal with the organism in an effort to duplicate the disease. In the case of human diseases, mammals such as rabbits, guinea pigs, and mice are typically used. However, finding the right animal subject may pose a problem, since not all animals are susceptible to human diseases. For example, armadillos must be used to study leprosy, because the more common laboratory animals are not susceptible to it. In the last of Koch’s procedures, the organism must be reisolated from the diseased animal. This step verifies the identity of the pathogen and confirms that it is the same as the original form. If the organism has been identified correctly as the cause of the disease, researchers can then proceed to learn more about the microorganism and its role in the disease process.
Identifying a pathogen as the cause of a specific disease and determining its biological characteristics aid medical researchers in finding prevention and treatment strategies. To cause illness, a microorganism must meet several criteria. First, it must survive transfer to the new host. Some pathogens can form protective structures, such as endospores, that will keep them alive outside a host for a long period of time. A pathogen that cannot survive outside a host must be passed directly in some way from an infected person to a healthy one. Second, a pathogen must overcome the host’s defenses. Some may enter through a wound, bypassing the skin barrier that protects the human body from many infections. Some produce chemicals that damage cells and weaken the body. Still others may be able to cause illness only if the host’s defenses are weakened by some factor such as age, malnutrition, or another existing illness. Finally, the organism must cause some damage to the host, resulting in the symptoms and signs associated with that illness. The disease process can best be understood by examining several examples of pathogens, the diseases they cause, and the strategies used against them.
The members of the genus
Clostridium
are all anaerobic, endospore forming, and toxin producing. Among the bacteria in this group are the pathogens that cause gangrene, tetanus, and botulism. Gangrene usually occurs when a wound has cut off the blood supply to an area of the body. Clostridium perfringens enters the body and is able to survive because the lack of blood has created an anaerobic condition. It produces a toxin that destroys surrounding tissue, allowing it to spread. Antibiotics may be effective in preventing the bacteria from spreading to healthy tissue, but because drugs are transported in the blood, they may not be able to reach the infected site. Placing the patient in a chamber containing oxygen under high pressure is one strategy used to destroy anaerobic bacteria.
Clostridium tetani also enters the body through a wound, sometimes a very small one. Since this organism is common and a small wound may go unnoticed, regular tetanus vaccinations are recommended. Once C. tetani bacteria enter the body, they produce a neurotoxin that causes the muscles to stiffen, resulting in a condition called tetanus, or lockjaw. In addition to antibiotics, an antitoxin must be given to neutralize the poison.
Clostridium botulinum causes botulism, a type of food poisoning. If proper canning techniques are not used, the endospores will germinate. The food then provides a medium on which they can grow, and the sealed can provides the perfect anaerobic conditions. C. botulinum produces a neurotoxin that, if it is not destroyed by adequate cooking, will produce neurological symptoms such as double vision and dizziness. If the disease is not treated with an appropriate antitoxin, death from respiratory failure can occur in a matter of days.
The human intestine contains large numbers of microorganisms. Some of them provide benefits to their host by producing vitamins and inhibiting the growth of other, potentially harmful microorganisms. Disease can result if the balance is changed. Escherichia coli, part of the normal intestinal flora, can cause infections when it is transferred to another part of the body, such as the urinary bladder. In developing countries, E. coli bacteria contaminate drinking water in such large numbers that they result in infantile diarrhea, a common cause of death in those countries. A 1993 epidemic in the United States involved a particularly virulent strain of E. coli that had been ingested in improperly cooked ground beef. The characteristics of the strain and the large number of bacteria in the meat disrupted the intestinal balance of those who ingested it, causing hundreds of people to become ill and resulting in the deaths of three young children.
The use of antibiotics can disrupt the natural balance by destroying beneficial bacteria as well as pathogens. Candida albicans, a yeastlike fungus, is part of the normal human flora. Its growth in the intestine is controlled by certain kinds of bacteria. When antibiotics are used, these beneficial bacteria are destroyed, and the Candida begins to multiply, resulting in a fungal infection known as candidiasis. The infection is not necessarily limited to the intestines; it may spread to the vagina, where it is commonly known as a yeast infection, or any other part of the body where Candida can be found. Strategies used to restore the balance may involve eating yogurt or capsules containing Acidophilus, one of the beneficial bacteria. Sugars, an important source of food for yeast, should be eliminated from the diet. If these measures do not work, antifungal medication may have to be used.
Fungi that cause skin infections such as athlete’s foot are called dermatophytes, and the resulting infection is called dermatophytosis. When an infected person takes a shower, dermatophyte spores are left in the shower stall. The warm, moist environment then allows the spores to survive until a potential new host comes. Since feet are usually enclosed in shoes and socks, the dermatophytes are again provided with an ideal warm, moist environment. Prevention strategies involve using fungicidal disinfectants to kill the spores and wearing sandals in the shower to avoid coming in contact with the spores. Treatment includes antifungal medication and making the environment less suitable for fungi by keeping the feet dry.
Protozoa are also vulnerable to dry conditions. Entamoeba histolytica, the cause of amebic dysentery, is usually ingested in contaminated water. It can form cysts, which allows it to resist drying and freezing. An individual can become ill after eating food rinsed in contaminated water or drinking a “safe” beverage containing ice made from contaminated water.
Plasmodium species are responsible for malaria, which kills two million people in the world each year. Because this protozoan cannot live outside a host, it is dependent on the female Anopheles mosquito to transmit it from one person to another. When a mosquito “bites,” it pierces the skin with a hypodermic-like mouth and injects a local anesthetic to prevent the host from feeling its presence. At the same time, if it is infected with Plasmodium, it will inject malarial parasites into the bloodstream. These parasites spend most of their life cycle inside red blood cells, where they are protected from normal immune defenses. Once they have multiplied, they rupture the cells as they leave. Treatment involves maintaining sufficiently high levels of medicine, such as quinine, in the plasma that the parasites die. The most important public health strategy is to control the mosquito population in order to prevent transmission.
After bacteria, viruses are the most common pathogens. Their mode of transmission from one host to another depends on the type of virus. Some can survive for a long period of time outside a host, others must be transferred quickly through the air or by physical contact, and still others can survive only when passed directly into the host via bodily fluids or insect bites. The damage done to the host depends on the type of tissue that is infected by the virus. For example, the Epstein-Barr virus invades the lymphatic system, where it causes the enlarged lymph nodes and abnormal lymphocytes that are characteristic of mononucleosis. It is also associated with Burkitt lymphoma and Hodgkin disease, both cancers of the lymphatic system. HIV invades the T lymphocytes, the white blood cells that are crucial to the functioning of the immune system. Damage to the immune system not only makes the individual vulnerable to disease organisms coming from outside the body but also disrupts the balance between the host and normal human flora. This allows other viruses, bacteria, protozoa, and fungi such as Candida to multiply and cause potentially fatal secondary infections.
Perspective and Prospects Infectious diseases have had devastating effects on human populations and societies. For example, during the eighty-year period starting in 1347, recurrent plague epidemics resulted in the deaths of 75 percent of the European population. For many centuries, some physicians and others hypothesized that invisible creatures were the cause of disease. In 1546, Venetian physician Girolamo Fracastoro suggested the presence of germs (seeds) of disease that could be passed from person to person. Because these creatures could not be seen, this “germ” theory was not widely accepted. Then, in 1673, Dutch tradesman and inventor Antoni van Leeuwenhoek began sending descriptions and pictures of what he called “animalcules” to the Royal Society of London. An amateur scientist, Leeuwenhoek made simple microscopes and systematically studied the objects and materials around him. His discoveries of what are now known to be protozoa and bacteria were verified, and they opened the field of microbiology as a science.
Using their new knowledge of the microbial world, nineteenth-century researchers began to reexamine the germ theory of disease. In 1857, Louis Pasteur, a chemist, discovered that certain bacteria caused wine to spoil. A few years later, he isolated a protozoan as a cause of a silkworm disease and predicted that microbes could cause human illness. In 1875, Robert Koch, the inventor of Koch’s postulates, devised a procedure by which he demonstrated that anthrax was caused by a specific type of bacterium, Bacillus anthracis. His experiments led to widespread acceptance of the germ theory of disease, and his procedures provided a systematic method by which researchers could identify those germs. The twenty-five years that followed are referred to as the golden age of microbiology; during this time, one by one, nearly all the major bacterial pathogens were identified.
During this intense period of discovery, researchers soon found that although fine porcelain filters were used to trap microorganisms, in some cases the liquid filtrate was capable of causing disease. The term “virus,” meaning poison, was used because it was thought at first that the liquid contained a toxic substance. Pasteur hypothesized that there might be an organism too small to be seen using the light microscope. Later, this was verified when researchers were able to remove the water from the filtrate, leaving crystals behind. After the invention of the electron microscope in 1933, individual virions could be seen.
The discovery of pathogens quickly led to research aimed at finding ways to prevent and treat infectious diseases. The contagious nature of disease was known in ancient times, as illustrated by the practices of Greek physicians and Jewish hygiene laws. Prior to Koch’s work, Hungarian physician Ignaz Philipp Semmelweis in the 1840s and English physician Joseph Lister in the 1860s showed that antiseptic techniques could control transmission of diseases. In 1849, English physician John Snow traced the source of a cholera epidemic to a single water pump in London. The knowledge that a specific pathogen was involved made it possible for more specific means of prevention to be applied. Within ten years of Koch’s report, Pasteur developed vaccines for anthrax and rabies. Immunizations for many infectious diseases were developed, public sanitation measures were taken to reduce the contamination of food and water, and surgeons adopted techniques to control surgical and wound infection.
Although progress in disease prevention was being made, once a person became ill, treatment was still primarily a matter of keeping the patient alive until the disease ran its course. In the early twentieth century, a German physician named Paul Ehrlich began to search for what he called a “magic bullet”—a chemical that would specifically treat a disease by killing the pathogens that caused it. After several years of work, compound 606, an arsenic derivative, was made available to treat syphilis. Sulfa drugs were developed in the 1920s. In 1929, Alexander Fleming discovered penicillin, a substance produced by the mold Penicillium that could destroy bacteria in cultures. In 1939, Ernst Chain and Howard Florey used penicillin successfully to treat bacterial infections. In 1944, Selman Waksman discovered streptomycin and used the term “antibiotic” to refer to a substance manufactured by a living organism that kills or inhibits the growth of a pathogen.
By the 1970s, it seemed that the end of infectious disease as a major medical problem was in sight. Several developments brought an end to this complacency. Antibiotic-resistant strains of bacteria such as
Staphylococcus
and the causative agents behind gonorrhea and syphilis appeared and soon became widespread. Childhood diseases that were once thought to be under control reappeared as a result of neglected vaccination programs. Increased world travel also facilitated the spread of disease from country to country. Then, in 1981, AIDS was first described; within a few years, it became a worldwide health problem. As people with AIDS began to succumb to previously uncommon secondary diseases, these diseases had to be studied. A new antibiotic-resistant strain of tuberculosis also appeared as a direct result of the AIDS epidemic. These developments have reemphasized the study of microbiology and demonstrated its importance to human health.
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