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Using less antibiotics is not enough to stop resistant bacteria, study finds

For people wary of using too many antibiotics, a recent Duke study offers some worrisome news.

The study—published in the journal Nature Communications—focused on a phenomenon called horizontal gene transfer, which refers to the ability of bacteria to transfer genes from one bacterium to another, to show that reducing the usage of antibiotics may not be enough to stop the spread of resistant bacteria. Resistant bacteria can swap genes with non-resistant bacteria fast enough that the antibiotic resistance gene can thrive even when antibiotic usage is reduced, the paper states.

“We’re not claiming at all to say that reduced antibiotic use is not useful—on the contrary, it’s very useful, it’s very critical,” said Lingchong You, Paul Ruffin Scarborough associate professor of engineering and the senior author of the paper. “In addition to that, what we’ve also discovered is that to make the overall strategy more effective, we may also need to develop strategies to directly target horizontal gene transfer.”

Genes that confer resistance to antibiotics are typically located on a mobile, circular piece of DNA known as a plasmid, explained Allison Lopatkin, a former graduate student in You’s laboratory—the Laboratory of Biological Networks—and current postdoctoral fellow at the Massachusetts Institute of Technology.

This means that resistant bacteria can send their antibiotic-resistant DNA to other bacteria, thereby causing those bacteria to become resistant as well. Lopatkin added that the speed of this transfer is astonishing.

“That literally means that bacteria are sharing their genes among one another, so think of it as if you were to pet your dog and grow a tail the next day—that’s how different these bacterial species are,” she said. “They can swap genes readily, in a matter of minutes even.”

However, Lopatkin explained that possessing this resistance-conferring plasmid does come with a cost. Resistant bacteria typically grow more slowly because of the proteins being produced to fight off the antibiotic.

A prior hypothesis stated that removing the antibiotic from the bacterial environment would cause non-resistant—or sensitive—cells to thrive while causing the resistant cells to dwindle, she explained. In other words, when there is no antibiotic present, the resistant bacteria no longer have an advantage over the sensitive type.

“The idea is that if you remove antibiotic selection, you don’t favor the cells that carry the burden—that carry that plasmid,” she said. “We should theoretically see the sensitive cells overtake the population and displace the resistant cells, and basically, resistance would go away.”

The paper’s findings call this hypothesis into question by showing that horizontal gene transfer can even the playing field between resistant and sensitive bacteria. You explained that the plasmid was able to spread fast enough so that the resistance was maintained even in an environment without antibiotics.

This showed that merely reducing the amount of antibiotics prescribed—an “incredibly important” initiative nonetheless—would be insufficient in preventing the growth of resistant bacteria. Instead, a different type of treatment would need to be introduced to address horizontal gene transfer.

Lopatkin mentioned that some hopeful evidence appeared in an otherwise dismal study—employing a cocktail of drugs known to interfere with horizontal gene transfer showed promise in reducing the spread of resistance. The drugs reversed the resistance in four out of the nine plasmids tested and prevented the transfer of another four, she added. 

In the future, the researchers hope to continue examining the role of horizontal gene transfer in bacterial resistance.

“Moving forward, a really great place to start would be to partner with industry and do some sort of high-throughput screening for chemicals,” Lopatkin said.

High-throughput refers to using automated machines to conduct tests very rapidly to test whether a large number of chemicals would be effective.

She explained that this would shed light on the most potent combination of molecules that could be harnessed to target resistant bacteria spreading their DNA. It is also important to examine the effects of these drugs on the gut microbiome—where horizontal gene transfer is commonplace—to ensure that there will not be any harmful effects on the human body’s natural functions, Lopatkin noted.

You added that this study was performed on a relatively small scale, but that it would be important to “investigate the dynamics in more complex communities” to analyze “to what extent our results with a limited number of bacterial populations can be generalized to a larger setting.”


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