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The World of Darwin
Resistance to Antibiotics
Resistance to Antibiotics
Up until the Second World War, bacteria had had things very much their own way. Only the immune system stood between humans and thousands of disease causing bacteria. Then Howard Florey in England showed that penicillin, a compound produced by one of Sir Alexander Fleming's molds, could be sent into battle against these tiny invaders.

Use of penicillin marked a major turning point in therapeutic medicine, and antibiotics have become our first line of defense against many diseases.

Unfortunately, natural selection and evolution have prevented antibiotics from wiping out illness caused by bacteria and giving us a disease-free world. Despite their simplicity and apparent genetic homogeneity, many bacteria carry small circles of DNA on which genes can change rapidly.

These genes can mutate and alter their function without harming the ability of the bacteria to grow and reproduce. In this way, they provide a pool of variation somewhat similar to the variants of genes found in higher organisms.

When an antibiotic floods a person's body, millions and millions of sensitive bacteria die, taking their genes with them. Somewhere, however, in the vast population of bacteria in the human body, one cell has just the right mutation to change a protein in just the right way so it can fight off the killing action of the drug.

Once this protein in altered, the bacterium can live in the presence of the antibiotic. Resistance to the killing action of the chemical enables this one cell to grow, divide and reproduce under the new environmental conditions in which all its relatives have died.

The gene for antibiotic resistance, therefore, has a positive effect on the survival of a bacterium when the antibiotic is present.

Unharmed by the new environmental circumstances, the resistant bacteria take over and dominate the population by growing and dividing unchecked. Eventually, all the bacterial cells become resistant, rendering that particular antibiotic useless as a therapeutic agent for that person.

Some forms of syphilis, a worldwide killer, cannot now be controlled by penicillin any longer. All the cells causing this disease are now resistant. Medical authorities regard the steady increase in bacterial infections that cannot be treated with antibiotics as the most serious problem facing world health.

Although bacterial resistance to antibiotics sounds like a classic example of natural selection at work, the results could be explained in another way. The antibiotic itself could have acted on the bacterial population and caused a shift towards antibiotic resistance.

Experiment One: To test this alternative hypothesis, scientists carried out two experiments. A flask of growing bacteria was diluted with sterile salt solution and small samples were transferred to test tubes.

If the dilution was correct, each new test tube contained a single bacterial cell capable of growth into a new population. Before the bacteria began to grow, however, an antibiotic was added to each tube and all tubes were placed in a warm incubator under perfect growth conditions.

When the tubes were examined the next day, most of the bacteria had died, killed by the antibiotic against which they had no protection. But, every once in a while, one tube was seen to be filled with growing cells.

When these cells were tested, they all showed resistance to the antibiotic. So far, this experiment had simply duplicated the conditions seen in the human body and confirmed those results.

Figure legend: Natural Selection 1. A single bacterium is placed in every test tube along with an antibiotic. Those bacteria with antibiotic-resistance genes survive, the sensitive bacteria die.
A second experiment, however, showed that variation followed by natural selection could explain these observations.

Experiment Two: Starting again from the beginning, scientists placed single bacterial cells into separate test tubes. This time, however, they allowed the bacteria to grow into new populations before adding anything to the tubes.

Once each tube was full of bacteria (that had grown from a single cell), and antibiotic was added and all the sensitive cells were killed.

Occasionally, however, in one tube the antibiotic had no effect and all the cells in that tube were found to be resistant to the killing action of the drug, just as they had been in the first experiment.

Clearly, the second experiment shows that the gene for antibiotic resistance came first. A small variation in the base sequence of the DNA produced a variant gene that enabled the bacterium to defeat the killing action of the antibiotic. Alone in its test tube, this bacterium showed the "bottleneck" effect and passed on its genotype to all is descendants.

Later, when the antibiotic was added to the tubes, the cells without this saving gene died (they were less fit), but the descendants of the resistant cell lived on (they were more fit). Variation in the available genotypes followed by an environmental change (adding the antibiotic) had brought about the natural selection of the fittest gene combination.

Figure legend: Natural Selection 2. In this second experiment, each individual bacterium grows into a population of identical individuals before the antibiotic is added.

As with the first experiment, the sensitive bacteria die and those bacteria with the mutated, antibiotic-resistance gene survive.

This experiment shows that the mutation came first and was then followed by environmental selection.

© 2001, Professor John Blamire