Increasing tolerance to antibiotics is the most widely known and appreciated kind of pathogen evolution. Since their discovery in the 1950s, an enormous number of studies have established many med- ically important conclusions:
1. Bacterial resistance to antibiotics arises not by the gradual development of tolerance by individual bacteria but by rare gene mutations or new genes introduced by plasmids.
2. Gene mutations can be transmitted by plasmid infection or other processes to different species of bacteria.
3. The presence of an antibiotic causes the initially rare mutant strain to increase and gradually replace the ancestral type.
4. If the antibiotic is removed, ancestral strains slowly replace the resistant forms.
5. Mutations within a resistant strain can confer still greater resistance, so that increasing the dose of an antibiotic may be effective only temporarily.
6. Low concentrations of an antibiotic, which may retard bacterial growth only slightly, will eventually select for strains that resist the slight retardation.
7. Mutations that confer still higher levels of resis- tance arise in such partially adapted strains more often than in the original nonresistant strain.
8. Resistance to one antibiotic may confer resistance to another, especially if the two are chemically related.
9. Finally, the disadvantage of resistant strains in the absence of an antibiotic is gradually lost by further evolutionary changes, so that resistance can pre- vail even where no antibiotics have been used for a long time.
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