Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [55]
Antibiotics, scientists discovered, kill bacteria in many ways. Some attack enzymes that help replicate DNA. Others, such as penicillin, interfere with the construction of the peptidoglycan mesh that wraps around E. coli and other bacteria. Gaps in the mesh form, and the high-pressure innards of the microbes burst out. Organisms naturally make only trace amounts of antibiotics, but drug companies began to produce them in enormous bulk, rearing fungi and bacteria in giant fermenters or synthesizing drugs from scratch. It would take billions of microbes to produce the antibiotics in a single pill. In such a concentrated form, antibiotics had a staggering effect on disease-causing bacteria. They didn’t just reduce infections. They got rid of them altogether, and with few noticeable side effects. The war against infectious diseases seemed to have suddenly become a rout.
But even in those heady days of early victory, there were signs of trouble. At one point in their research, Florey and Chain discovered that their cultures of mold had been invaded by E. coli. The bacteria were able to survive in a soup of penicillin by producing an enzyme that could cut the antibiotic molecule into feeble fragments.
As penicillin was being introduced to the world, microbiologists were discovering how mutations arose in E. coli. In 1943, Delbrück and Luria showed that mutations spontaneously made E. coli resistant to viruses. In 1948, the Yugoslavian-born geneticist Milislav Demerec showed that the same held true for antibiotics. He bred resistant strains of E. coli and Staphylococcus aureus. Both species became increasingly resistant as they picked up a series of mutations. In the same year that Demerec published his results, doctors reported that penicillin was beginning to fail in their Staphylococcus-infected patients.
These disturbing discoveries did nothing to halt the rise of antibiotics. Today the world consumes more than ten thousand tons of antibiotics a year. Some of those drugs save lives, but a lot of them are wasted. Two-thirds of all the prescriptions that doctors hand out for antibiotics are useless. Antibiotics can’t kill viruses, for instance. Many farmers today practically drown their animals with antibiotics because the drugs somehow make the animals grow bigger. But the cost of the antibiotics is greater than the profit from the extra meat.
Along with the rise in antibiotics has come a rise in antibiotic resistance. Drugs that were once fatal to bacteria are now useless. E. coli’s story is typical. Resistant strains of E. coli first emerged in the 1950s. At first only a small fraction of E. coli could withstand any particular antibiotic, but over several years resistant microbes became more common. Soon the majority of E. coli could withstand the drug. As one drug faltered, doctors would prescribe another—a stronger drug with harsher side effects or a more recently discovered molecule. And in a few years that drug would begin to fail as well. Before long, strains of E. coli emerged that could resist many antibiotics at once.
E. coli uses many tricks to dodge antibiotics. As Florey and Chain discovered, it can secrete enzymes that cut penicillin into harmless fragments. In some cases, E. coli’s proteins have taken on new shapes that make it difficult for antibiotics to grab them. And in other cases, E. coli uses special pumps to hurl antibiotics out of its interior. For every magic bullet science has found for E. coli, E. coli has acquired an equally magic shield.
SKIN OF FROG
E. coli has evolved its resistance to antibiotics almost entirely out of view. It was not trapped in a laboratory flask, where a scientist could track every mutation from one generation to the next. Its flask was the world.
The pieces of evidence scientists have assembled are enough for them to reconstruct some of its history. The genes that now provide E. coli with resistance to antibiotics did not suddenly appear in 1950. They descend from older genes that originally had other functions. Some of the pumps that flush antibiotics