Microorganisms that are capable of causing disease are called pathogens. Although microorganisms that cause disease often receive the most attention, it is important to note that most microorganisms do not cause disease. In fact, many probably provide some protection against harmful microorganisms because they effectively compete with the harmful organisms for resources, preventing them from growing.
A true pathogen is an infectious agent that causes disease in virtually any susceptible host. Opportunistic pathogens are potentially infectious agents that rarely cause disease in individuals with healthy immune systems. Diseases caused by opportunistic pathogens typically are found among groups such as the elderly (whose immune systems are failing), cancer patients receiving chemotherapy (which adversely affects the immune system), or people who have AIDS or are HIV-positive. An important clue to understanding the effect of HIV on the immune system was the observation of a rare type of pneumonia among young men caused by Pneumocystis carinii, an organism that causes disease only among the immunosuppressed.
Infection and Disease
The terms "infection" and "disease" are not synonymous. An infection results when a pathogen invades and begins growing within a host. Disease results only if and when, as a consequence of the invasion and growth of a pathogen, tissue function is impaired. Our bodies have defense mechanisms to prevent infection and, should those mechanisms fail, to prevent disease after infection occurs. Some infectious agents are easily transmitted (that is, they are very contagious), but they are not very likely to cause disease (that is, they are not very virulent). The polio virus is an example: It probably infects most people who contact it, but only about 5 to 10 percent of those infected actually develop clinical disease. Other infectious agents are very virulent, but not terribly contagious. The terror surrounding Ebola hemorrhagic fever is based on the virulence of the virus (50 to 90 percent fatality rate among those infected); however, the virus itself is not transmitted easily by casual contact. The most worrisome infectious agents are those that are both very contagious and very virulent.
Host Invasion Pathways
In order to cause disease, pathogens must be able to enter the host body, adhere to specific host cells, invade and colonize host tissues, and inflict damage on those tissues. Entrance to the host typically occurs through natural orifices such as the mouth, eyes, or genital openings, or through wounds that breach the skin barrier to pathogens. Although some pathogens can grow at the initial entry site, most must invade areas of the body where they are not typically found. They do this by attaching to specific host cells. Some pathogens then multiply between host cells or within body fluids, while others such as viruses and some bacterial species enter the host cells and grow there.
Although the growth of pathogens may be enough to cause tissue damage in some cases, damage is usually due to the production of toxins or destructive enzymes by the pathogen. For example, Corynebacterium diphtheriae, the bacteria that causes diphtheria, grows only on nasal and throat surfaces. However, the toxin it produces is distributed to other tissues by the circulatory system, damaging heart, liver, and nerve tissues. Streptococcus pyogenes, the infectious agent associated with several diseases including strepthroat and "flesh-eating disease," produces several enzymes that break down barriers between epithelial cells and remove fibrin clots, helping the bacteria invade tissues.
Microbes That Cause Infectious Diseases
There are five major types of infectious agents: bacteria, viruses, fungi, protozoa, and helminths. In addition, a new class of infectious agents, the prions, has recently been recognized. A brief review of the general characteristics of each of these agents and examples of some diseases they cause follows.
Bacteria are unicellular prokaryotic organisms; that is, they have no organized internal membranous structures such as nuclei, mitochondria, or lysosomes. Their genomes are circular, double-stranded DNA that is associated with much less protein than eukaryotic genomes. Most bacteria reproduce by growing and dividing into two cells in a process known as binary fission. Despite these commonalities that group them together in the Kingdom Monera, there is a wide range of diversity among the bacteria.
There are a variety of morphologies among bacteria, but three of the most common are bacillus (rod-shaped), coccus (spherical), or spirillum (helical rods). The energy sources for bacteria also vary. Some bacteria are photosynthetic and obtain their energy directly from the sun. Others oxidize inorganic compounds to supply their energy needs. Still other bacteria generate energy by breaking down organic compounds such as amino acids and sugars in a respiratory process. Some bacteria require oxygen (aerobes), while others are unable to tolerate it (anaerobes). Some bacteria can grow either with or without oxygen (facultative anaerobes).
Bacteria are frequently divided into two broad classes based on their cell wall structures, which influences their Gram stain reaction. Gram-negative bacteria appear pink after the staining procedure. Familiar pathogenic gram-negative organisms are Salmonella typhi, which causes typhoid fever, and Yersiniapestis, which causes plague. Gram-positive bacteria appear purple after the Gram stain procedure. Examples of pathogenic gram-positive bacteria are Staphylococcus aureus, which causes skin, respiratory, and wound infections, and Clostridium tetani, which produces a toxin that can be lethal for humans.
Microbiologists have found viruses that infect all organisms, from plants and animals to fungi and bacteria. Viruses, however, are not organisms themselves because, apart from a host cell, they have no metabolism and cannot reproduce. A virus particle is composed of a viral genome of nucleic acid that is surrounded by a protein coat called a capsid. In addition, many viruses that infect animals are surrounded by an outer lipid envelope, which they acquire from the host cell membrane as they leave the cell. Unlike organisms, in which the genetic material is always double-stranded DNA, viral genomes may be double- or single-stranded DNA (a DNA virus), or double- or single-stranded RNA (an RNA virus).
In the general process of infection and replication by a DNA virus, a viral particle first attaches to a specific host cell via protein receptors on its outer envelope, or capsid. The viral genome is then inserted into the host cell, where it uses host cell enzymes to replicate its DNA, transcribe the DNA to make messenger RNA, and translate the messenger RNA into viral proteins. The replicated DNA and viral proteins are then assembled into complete viral particles, and the new viruses are released from the host cell. In some cases, virus-derived enzymes destroy the host cell membranes, killing the cell and releasing the new virus particles. In other cases, new virus particles exit the cell by a budding process, weakening but not destroying the cell.
In the case of some RNA viruses, the genetic material can be used directly as messenger RNA to pro duce viral proteins, including a special viral RNA polymerase that copies the RNA template to pro duce the genetic material for new viral particles. Other RNA viruses, called retroviruses, use a unique enzyme called reverse transcriptase to copy the RNA genome into DNA. This DNA then integrates itself into the host cell genome. These viruses frequently exhibit long latent periods in which their genomes are faithfully copied and distributed to progeny cells each time the cell divides. The human immunodeficiency virus (HIV), which causes AIDS, is a familiar example of a retrovirus.
Just like other infectious agents, viruses cause disease by disrupting normal cell function. They do this in a variety of ways. Some viruses make repressor proteins that stop the synthesis of the host cell's proteins, RNA, and DNA. Viral activity may weaken cell membranes and lysosomal membranes, leading to cell autolysis. Some viral proteins are toxic to cells, and the body's immune defenses also may kill virus-infected cells.
Viruses are classified using a variety of criteria, including shape, size, and type of genome. Among the DNA viruses are the herpes viruses that cause chicken pox, cold sores, and painful genital lesions, and the poxvirus that causes smallpox. Significant RNA viruses that cause human disease include rhinoviruses that cause most common colds; myxoviruses and paramyxoviruses that cause influenza, measles, and mumps; rotaviruses that cause gastroenteritis; and the retroviruses that cause AIDS and several types of cancer.
Fungi are eukaryotic, heterotrophic organisms that have rigid cellulose- or chitin-based cell walls and reproduce primarily by forming spores. Most fungi are multicellular, although some, such as yeasts, are unicellular. Together with bacteria, fungi fulfill the indispensable role of decomposers in the environment. Many fungi also infect plants and animals. Examples of diseases caused by fungi are ringworm and histoplasmosis (a mild to severe lung infection transmitted by bat or bird droppings). Yeasts of the Candida genus are opportunistic pathogens that may cause diseases such as vaginal yeast infections and thrush (a throat infection) among people who are immunocompromised or undergoing antibiotic therapy. Antibiotics reduce the bacterial population normally present in the throat and vagina, allowing the yeast to grow unchecked.
Protozoa are unicellular, heterotrophic eukaryotes that include the familiar amoeba and paramecium. Because protozoa do not have cell walls, they are capable of a variety of rapid and flexible movements. Protozoa can be acquired through contaminated food or water or by the bite of an infected arthropod such as a mosquito. Diarrheal disease in the United States can be caused by two common protozoan parasites, Giardia lamblia and Cryptosporidium parvum. Malaria, a tropical illness that causes 300 million to 500 million cases of disease annually, is caused by several species of the protozoan Plasmodium.
Helminths are simple, invertebrate animals, some of which are infectious parasites. They are multicellular and have differentiated tissues. Because they are animals, their physiology is similar in some ways to ours. This makes parasitic helminth infections difficult to treat because drugs that kill helminths are frequently very toxic to human cells.
Many helminths have complex reproductive cycles that include multiple stages, many or all of which require a host. Schistosoma, a flatworm, causes the mild disease swimmer's itch in the United States; another species of Schistosoma causes the much more serious disease schistosomiasis, which is endemic in Africa and Latin America. Schistosome eggs hatch in freshwater, and the resulting larvae infect snails. When the snails shed these larvae, the larvae attach to and penetrate human skin. They feed, grow, and mate in the human bloodstream; the damage to human tissues caused by the accumulating schistosome eggs with their sharp spines results in disease symptoms including diarrhea and abdominal pain. Liver and spleen involvement are common. Another disease due to a helminth is trichinosis, caused by the roundworm Trichinella spiralis. This infectious agent is typically ingested in improperly cooked pork from infected pigs. Early disease symptoms include vomiting, diarrhea, and fever; later symptoms include intense muscle pain because the larvae grow and mature in those tissues. Fatal cases often show congestive heart failure and respiratory paralysis.
During the past two decades, evidence has linked some degenerative disorders of the central nervous system to infectious particles that consist only of protein. These "proteinaceous infectious particles" have been named prions (preeons). The known prion diseases include Creutzfeldt-Jakob disease (in humans), scrapie (in sheep), and bovine spongiform encephalopathy ("mad cow disease" in cattle); all known prion diseases frequently result in brain tissue that is riddled with holes. While some prion diseases are inherited, others are apparently due to infection by eating infected tissue or inadvertently through medical procedures such as tissue transplants.