How Bacteria Become Resistant to Antibiotics

Two years ago, researchers in the biomedical engineering department at Boston University found that lethal doses of antibiotics can stimulate the production of reactive oxygen species molecules, free radicals that damage DNA, and protein and lipids in bacterial cells.

reactive oxygen species (ROS) molecules, free radicals that damage DNA, and protein and lipids in bacterial cells. Now, the same group of researchers has found that the free radicals produced in targeted bacteria by a sub-lethal dose of an antibiotic “live on to accelerate the formation of mutations that protect against a variety of antibiotics other than the administered drug

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E. coli

Staphylococcus

BME graduate student Michael Kohanski, and post-doc Mark DePristo administered sub-lethal doses of five different kinds of antibiotics to strains of and . The different antibiotics increased levels of ROS and mutations in the bacterial DNA. In the second step, the researchers performed experiments “to show that bacteria initially subjected to a sub-lethal dose of one of the antibiotics exhibited cross-resistance to a number of the other antibiotics — and in some cases, no resistance to the initially-applied antibiotic.” Finally, the team sequenced bacterial genes that were known to cause resistance to each of the antibiotics, which enabled them to pinpoint mutations in the genes that were believed to be crucial in protecting against the antibiotic.

Lead researcher James Collins, a professor in the BME department,

“The sub-lethal levels dramatically drove up the mutation levels, and produced a wide array of mutations,” Collins said. “Because you’re not killing with the antibiotics, you’re allowing many different types of mutants to survive. We discovered that in this zoo of mutants, you can actually have a mutant that could be killed by the antibiotic that produced the mutation but, as a result of its mutation, be resistant to other antibiotics.”

According to the researchers, the findings could have direct consequences for the way that the general population sometimes administers antibiotics in low or incomplete doses.

Two years ago, researchers in the biomedical engineering (BME) department at Boston University found that lethal doses of antibiotics can stimulate the production of