Appendix B. Microbial Life Forms

Bacteria Lack Nuclei and Other Organelles

Bacteria cause some of our most notorious infectious diseases: plague, typhus, tuberculosis, and cholera are entries on a long list. These microbes are minute, single-celled organisms that contain all the information needed to reproduce. Bacteria reproduce by binary fission (splitting apart). DNA is duplicated and pulled to separate halves of the cell; then a ring forms in the cell wall, much like a ring on your finger. The ring gets tighter and tighter until it pinches the cell in two. After cell division, the two daughter cells grow until they, too, divide in half. Thus, the number of cells in a bacterial culture increases by doubling: 1, 2, 4, 8, 16, 32, 64, and so on. With some bacteria, the doubling time can be as short as 20 minutes, which enables a culture to go from one cell to a million in 7 hours. Such rapid growth makes it important to treat an infection promptly. Other bacteria grow more slowly (the tuberculosis bacillus takes 24 hours to double), but they can be just as deadly.

Bacteria are called prokaryotic organisms because their DNA is not packaged in a true nucleus, a microscopic membrane-bound structure seen in cells of higher organisms such as ourselves. (Cells with a nucleus are called eukaryotic.) This difference between prokaryotic and eukaryotic organisms reflects evolutionary paths that separated roughly two billion years ago. Over that time even highly conserved aspects, such as the machinery for making proteins, changed enough for antibiotics to block bacterial growth with little effect on our cells.

Most bacterial species are not pathogens. When we treat with antibiotics for a harmful bacterium, we also eliminate helpful ones. The resulting disturbance of the microbial ecosystem in our bodies can enable other harmful microbes to take over. Treatment with antibiotics has risk.

Fungi Are Eukaryotes Having Cell Walls But Not Chloropasts

Yeasts, molds, and mushrooms are fungi. Unlike bacteria, fungal cells store their DNA in true nuclei. Such subcellular structures, called organelles, localize particular cellular functions. For example, mitochondria are power plants that convert chemical energy from sugars into molecules such as ATP. Lysosomes are the cellular equivalent of garbage disposal units. They are filled with enzymes that destroy other macromolecules. Bacterial cells lack such localization of cellular activity.

In general, the molecules that constitute fungal cells are similar to those of human cells. Consequently, antibiotics that attack bacteria usually fail to affect fungi, largely because the agents were designed to have little activity against eukaryotic organisms. However, fungal cells do differ from our cells in fundamental ways that can be exploited. One of those differences involves the structure of the cell membrane. Most clinical antifungal agents target enzymes that participate in making components of the membrane.

Yeasts are single-celled fungi that grow much like bacteria. Liquid cultures become cloudy when many yeast cells are present, and yeast form colonies on agar. Some yeast species reproduce by dividing (fission yeast), whereas others form buds that break off and grow into new cells. (A bud is a protrusion of the cell that gradually increases in size until it pinches off.) Bakers’ yeast, commonly used to make bread, is one of the most thoroughly studied eukaryotic organisms. Its cousin, Candida albicans, kills immune-deficient persons.

We often think of molds as the fuzzy green or black growth on old bread. Molds are multicellular organisms whose bodies consist of long, thin filaments called hyphae. Some hyphal cells develop into fruiting bodies full of tiny spores. The spores are released into the air; by breathing, we draw them deep into our lungs. There, they germinate and sprout hyphae that penetrate our lung tissue. Some filamentous fungi convert to a yeast form in our lungs, a conversion crucial for their invasion of our lung tissue (see Box B-1).

Yeasts and molds are everywhere in our environment. For most persons, they are not a problem because healthy immune systems remove fungal cells from our bodies. However, as our populations age and immunosuppression becomes increasingly common, fungal diseases also become increasingly common. Invasive fungal infections are now a major cause of death for cancer patients. In some types of patient, fungal infections account for nearly half the deaths. Newborns are also susceptible to yeast infection, because their immune systems are poorly formed.

Parasitic Protozoa Are Eukaryotes Lacking a Cell Wall

Protozoa are small, single-celled organisms found in many environments. Several species parasitize humans, causing serious diseases such as malaria and sleeping sickness. Inside human hosts, parasitic protozoa often have complex life cycles, with distinct forms in liver and blood. Some of these protozoa have still another distinct form when inside an insect, usually a mosquito or biting fly. This is the stage that spreads when a person is bitten by the insect. Malaria, which is caused by four distinct parasite species, is a major killer in countries unable to control mosquitoes (the World Health Organization estimated 246 million malaria cases in 2006 with almost 900,000 deaths). Malaria is such a devastating disease that humans in Africa and the Mediterranean basin have acquired mutations, such as sickle-cell trait, that provide partial protection. (Sickle-cell trait is a genetic condition in which one of the two copies of a hemoglobin gene is mutant; when both copies are mutant, the affected person suffers from sickle-cell disease.)

Helminths Are Parasitic Worms

Parasitic worms (helminths) are multicellular organisms that live inside humans and animals. Worm offspring are passed to human hosts through poorly cooked meat, contaminated water, and mosquitoes. Toxins produced by the worms can increase host susceptibility to a variety of other infections. While diseases caused by parasitic worms are rare in the U.S. and other industrialized countries, they commonly result in blindness and dysentery in developing countries. Pinworms are the most common helminth infection; in the U.S. they frequent travelers, migrant laborers, and the homeless.

Viruses Are Inert Until They Infect

In molecular terms, viruses are much simpler than cellular pathogens and parasites. They are composed of a nucleic acid, either RNA or DNA, a protein coat that protects the nucleic acid, and often several other proteins that form an outer envelope. Some viruses also carry important enzymes with them. The protein coat of viruses can be simple, or it can comprise many proteins that form the complex head and tail structures seen with some bacteriophages (viruses that attack bacteria). Other viruses, such as human immunodeficiency virus (HIV), acquire an outer coat of membrane when they exit human cells (release of virus occurs by the infected cells forming small buds that pinch off, releasing membrane-coated virus). We stress that no virus makes its own proteins; consequently, all viruses seek out living cells and force them make viral proteins and new copies of viral nucleic acids. In some cases, the viruses take the host protein synthesis machinery for their own exclusive use. In other cases, the host cell is allowed to continue making its own proteins.

Some viruses kill their host cells outright, while others have the option of entering a dormant state. That dormant state can involve insertion of viral DNA into the host chromosome. When conditions change, the virus can literally pop its DNA out of the host chromosome. Such occurs with some bacterial viruses. After the viral DNA excises from the chromosome, it duplicates, viral proteins are produced that combine with the DNA to make new infectious virus particles, and then other viral proteins break open the host cell. HIV enters its host cell as an RNA virus, converts its genetic information to a DNA form, and then inserts that DNA into a host chromosome. HIV DNA stays in the host chromosome until the host dies. From its chromosomal location, HIV DNA directs formation of new virus parts, including copies of viral RNA for new virus particles. In each of these scenarios, viral genes encode viral proteins that enable the virus to reproduce.