Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [62]
At first the spread of resistant Shigella followed the pattern mapped out in other bacteria, with mutations giving rise to powerful new genes that gave individual microbes a reproductive edge. But then something startling happened. Shigella strains emerged that were resistant to all the antibiotics. Their transformation was sudden: if doctors gave a victim of Shigella a single type of antibiotic, the bacteria often became resistant not only to that drug but to other antibiotics the patient had never taken.
To make sense of this strangeness, Japanese scientists turned to Joshua Lederberg’s discovery of sex in E. coli a few years earlier. Lederberg had shown that on rare occasion the bacteria could transmit some of their genes to unrelated bacteria. In his experiments, ringlets of DNA—plasmids—moved from one microbe to another, dragging parts of the chromosome with them. Lederberg and other researchers had also discovered that prophages—those quiet viruses—could shuttle genes as well. A roused virus sometimes accidentally copied genes from its host into its own DNA and carried them to other bacteria. Lederberg and other scientists won Nobel Prizes for their discoveries, but for years most scientists considered this “infective heredity” only a convenient laboratory tool. It was not an important part of the natural world. They were wrong, and the dysentery outbreaks in Japan offered the first proof.
Tsutomo Watanabe at Keio University in Tokyo and other Japanese scientists explored the possibility that infective heredity was behind the rise of resistant Shigella. They proved that E. coli K-12 and Shigella could trade resistance genes. Experiments on patients infected with Shigella brought similar results. Watanabe concluded that the heavy use of antibiotics had spurred the evolution of resistance genes, either in Shigella or in another species of bacteria that lived in the gut. On rare occasion, a resistant microbe passed its genes to another species. These genes, later research would show, were carried on plasmids.
With each new antibiotic that Japanese doctors began to use on their patients, new resistance genes evolved, and their plasmids also spread among the bacteria of Japan. Sometimes a microbe would wind up infected with two plasmids at once, each carrying a gene for resistance to a different drug. The two plasmids swapped genetic material, producing a new ring of DNA carrying two resistance genes instead of one. Natural selection now favored the new plasmids even more, because they allowed bacteria to survive either drug. And over time the plasmids kept picking up other resistance genes. Eventually they made Shigella impervious to anything doctors tried to throw at it.
Few scientists outside Japan knew of these discoveries until 1963, when Watanabe wrote a long article in English for the journal Bacteriological Review. Western scientists were taken aback. They followed up with experiments of their own and confirmed that Watanabe was onto something big. Genes can shuttle between bacteria by many routes. Plasmids deliver some of them, but viruses deliver them as well. They accidentally incorporate some host genes into their own genome, which the viruses then carry to new hosts that they infect. Sometimes bacteria simply slurp up the DNA that spills out when other microbes die. These resistance genes can shuttle between individuals of the same species, and they sometimes leap from one species to another.
Horizontal gene transfer, as this genetic leaping is now known, works best in places where bacteria are packed in tight quarters. Many genes shuttle between microbes inside our bodies, as well as inside the bodies of chickens and other livestock that are fed antibiotics. Even houseflies that pick up E. coli can become a gene market. Horizontal gene transfer allows genes to leapfrog from microbe to microbe across staggering distances. In the jungles of French Guiana, scientists have found antibiotic-resistant E. coli in the guts of Wayampi Indians, who have never taken the drugs.