bacteria to resist specific host immune mechanisms; and they provide the bacteria with a competitive advantage by inhibiting other microorganisms in the host.
The evolution, ab initio, of virulence by mutations would be an extraordinarily complex chain of events and is more often inferred as a natural process than observed in the laboratory. Resistance to antibiotics and to serum bactericidal factors, however, is a unit step often seen in experiments. More often, virulence genes can be characterized by their transmission from one cell to another.
Virulence factors vary from organism to organism and can often be transferred among receptive bacteria by bacteriophages and plasmids. This movement of genetic material is one way that bacteria cope with changes in their surroundings, such as the presence of antibodies or phagocytic cells. Bacteria may possess more than one virulence factor, including toxins (neuro-, entero-, endo-, cyto-, erythrogenic, etc.), enzymes, colonization factors, adhesins, bacteriocins, hemolysins, and cell invasion and drug resistance factors (see Table 2-4).
In addition to the versatility afforded by gene transfer, an unexpected plasticity has been found in bacteria that amplifies particular genes related to rapid growth or virulence (Terzaghi and O'Hara, 1990). Hence, salmonellae growing rapidly in rich media are genotypically different from those starved for specific carbon sources (Sonti and Roth, 1989). The same is true for cholera vibrios in their host environment compared with aqueous reservoirs (Mekalanos, 1983).
This plasticity has introduced new complications into the evaluation of pathogenicity of bacterial strains that have been stored in the laboratory, supporting the intuitions of a prior generation of medical bacteriologists. The underlying genetic mechanisms are still under study; it is not yet known whether they involve more than intense natural selection operating on large populations subject to modest rates of spontaneous mutation. Whatever the mechanism, the emergence of enhanced virulence potential is observed within time intervals measured in days or hours.
The most recent example of the emergence of a new disease that is likely to have been the result of a mutation causing enhanced virulence occurred in 1984. In that year, an outbreak of severe disease in 10 children, aged three months to eight years, occurred in a single town in São Paulo State in Brazil. Symptoms included high fever, vomiting, and abdominal pain, followed by the development of purpura and shock owing to vascular collapse. All 10 children died within 48 hours of the onset of the fever.
It was thought at first that the children had contracted meningococcal