Historical diarrhea bacteria blasted past antibiotics, scooped pre-resistance

Color-enhanced scanning electron micrograph showing Salmonella Typhimurium (red) invading cultured human cells.

As soon as scientists figured out how to harness the power of antibiotic drugs, bacteria hit back. Following clinical trials of penicillin around 1941, doctors documented the spread of penicillin-resistant Staphylococcus aureus among hospital patients in 1942. By the late 1960s, more than 80 percent of S. aureus bacteria isolated in and out of hospitals turned up resistant to the revolutionary drug.

It’s a common pattern that has led to the crisis of antibiotic resistance the world is now facing. In 1945, Alexander Fleming himself—the discoverer of penicillin—even warned of such “an era… of abuses,” in which strong public demand for antibiotics would drive bacterial resistance that render the “miraculous” drugs impotent.

But the problem is not just overuse in people. And sometimes, bacteria aren’t just one step behind—they may be one step ahead, according to a new study in the Lancet Infectious Diseases.

Genetic analyses of 288 bacterial isolates collected between 1911 and 1969 from 31 countries show that Salmonella developed resistance to an antibiotic several years before that drug even hit the market. The finding suggests that the diarrhea-causing bacteria were somehow primed to withstand the semi-synthetic antibiotic ampicillin before doctors could prescribe it in the early 1960s. Thus, overuse in humans didn’t drive the emergence of that resistance.

Instead, the authors speculate that overuse of a related antibiotic—penicillin G—in animals may be to blame. During the 1950s and 1960s, farmers used low doses of penicillin G to enhance the growth of poultry and pigs, as well as prevent infections in pigs. The authors, led by bacteriologist François-Xavier Weill of the Institut Pasteur in Paris, suspect that the low doses of the drug that lingered in the waste, water, and soil around farms may have spurred the development and spread of genes that make bacteria resistant to the antibiotic. Because ampicillin is a derivative of penicillin, it may have helped make them resistant to the newer drug, too.

“Although our study cannot identify a causal link between the use of penicillin G and the emergence of transmissible ampicillin-resistance in livestock, our results suggest that the non-clinical use of penicillins like [penicillin G] may have encouraged the evolution of resistance genes in the late…

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