A small minority of bacteria are pathogens

The late nineteenth century was a productive era in the history of medicine—a time when bacteriologists, chemists, and physicians proved that many diseases are caused by microbial agents. During this time, the German physician Robert Koch laid down a set of four rules for establishing that a particular microorganism causes a particular disease:

  1. The microorganism is always found in individuals with the disease.

  2. The microorganism can be taken from the host and grown in pure culture.

  3. A sample of the culture produces the same disease when injected into a new, healthy host.

  4. The newly infected host yields a new, pure culture of microorganisms identical to those obtained in the second step.

These rules, called Koch’s postulates, were important tools in a time when it was not widely understood that microorganisms cause disease. Although modern medical science has more powerful diagnostic tools, Koch’s postulates remain useful. For example, physicians were taken aback in the 1980s when stomach ulcers—long accepted and treated as the result of excess stomach acid—were shown by Koch’s postulates to be caused by the bacterium Helicobacter pylori (Figure 25.20).

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Figure 25.20 Satisfying Koch’s Postulates Robin Warren and Barry Marshall of the University of Western Australia won the 2005 Nobel Prize in Medicine for showing that ulcers are caused not by the action of stomach acid but by infection with the bacterium Helicobacter pylori.

For an organism to be a successful pathogen, it must:

Failure to complete any of these steps ends the disease cycle of a pathogenic organism. Yet in spite of the many defenses available to potential hosts, some bacteria are very successful pathogens. Pathogenic bacteria are often surprisingly difficult to combat, even with today’s arsenal of antibiotics. One source of this difficulty is their ability to form biofilms.

For the host, the consequences of a bacterial infection depend on several factors. One is the invasiveness of the pathogen: its ability to multiply in the host’s body. Another is its toxigenicity: its ability to produce toxins (chemical substances that are harmful to the host’s tissues). Corynebacterium diphtheriae, the agent that causes diphtheria, has low invasiveness and multiplies only in the throat, but its toxigenicity is so great that the entire body is affected. In contrast, Bacillus anthracis, which causes anthrax, has low toxigenicity but is so invasive that the entire bloodstream ultimately teems with the bacteria.

There are two general types of bacterial toxins: exotoxins and endotoxins. Endotoxins are released when certain bacteria grow or lyse (burst). Endotoxins are lipopolysaccharides (complexes consisting of a polysaccharide and a lipid component) that form part of the outer bacterial membrane. Endotoxins are rarely fatal to the host; they normally cause fever, vomiting, and diarrhea. Among the endotoxin producers are some strains of the proteobacteria Salmonella and Escherichia.

Exotoxins are soluble proteins released by living, multiplying bacteria. They are highly toxic—often fatal—to the host. Human diseases induced by bacterial exotoxins include tetanus (Clostridium tetani), cholera (Vibrio cholerae), and bubonic plague (Yersinia pestis). Anthrax is caused by three exotoxins produced by Bacillus anthracis. Botulism is caused by exotoxins produced by Clostridium botulinum; these exotoxins are among the most poisonous ever discovered. The lethal dose for humans of one exotoxin of C. botulinum is about one-millionth of a gram. Nonetheless, much smaller doses of this exotoxin, marketed under various trade names (e.g., Botox), are used to treat muscle spasms and for cosmetic purposes (temporary wrinkle reduction in the skin).