The conventional wisdom on why some antibiotics don’t work rests on the concept of persistence. A small subset of bacteria sometimes hides out and escapes the effects of the drugs meant to kill them. These persisters can then come back with a vengeance and may no longer respond to the same antibiotic, the theory goes.

For example, antibiotics are only partially effective against infections caused by the Salmonella bacteria. The persistence of that infection can lead to other conditions, such as typhoid fever.

Researchers from the University of Basel challenge the persisters theory in a Nature article. If their theory holds true, scientists developing new antibiotics to “mop up” those recalcitrant bugs may want to reconsider their approach.

Read More: Antibiotic-Resistant Bacteria: What They Are and How Scientists Are Combating Them

The Persistence of Bacteria

“Contrary to widespread belief, antibiotic failure is not caused by a small subset of persisters. In fact, the majority of Salmonella in infected tissues are difficult to kill,” Dirk Bumann, a researcher from the University of Basel’s Biozentrum, said in a press release. “We have been able to demonstrate that standard laboratory tests of antimicrobial clearance produce misleading results, giving a false impression of a small group of particularly resilient persisters.”

For many years, researchers believed that a small subset of dormant bacteria are the main problem in fighting infections. These so-called persisters can survive antibiotic treatment and cause relapses later. Researchers worldwide have been working on new therapies aimed at targeting and eliminating these sleeping bacteria.

In a new study, Dirk Bumann’s team from the Biozentrum of the University of Basel challenges the prevailing concept that persisters are the cause of antibiotic ineffectiveness. So, if natural persistence doesn’t keep pesky bacteria around, what does?

To find out, the Swiss team monitored how both mice and tissue-mimicking lab models affected Salmonella survival. They suspect that, when the body fights an infection, it reduces the number of nutrients available to the invader.

Nutrition Plays Role in Bacteria Survival

Why would this be a bad thing? If bacteria need nourishment to survive, wouldn’t limiting or cutting it off also take out the bacteria? The answer is counter intuitive.

“Under nutrient-scarce conditions, bacteria grow very slowly,” Bumann said. “This may seem good at first, but is actually a problem because most antibiotics only gradually kill slowly growing bacteria.”

As a result, the bacteria hang around, even though they are under attack. For the study, the scientists monitored antibiotic action in single bacteria in real time. They observed that a large amount of the entire Salmonella population survived the treatment — not just a small subset of persisters.

By contrast, previous methods that measure bacterial survival against antibiotics have used indirect and delayed measurements, as opposed to the Swiss group’s real time approach. This has produced distorted or inaccurate results for years. Those results have falsely fed the persister narrative.

As a result, Bumann would like to see antibiotic resistance research emphasis shift. There should be more attention paid to bacterial nutrition and less on rooting out the persisters, Bumann said. Researchers will need to change both the technology they use and the assumptions about what they are looking at.

“In a few years, modern methods like real-time single-cell analysis will hopefully become standard,” Bumann said.

Read More: Why Flat Cell Imaging Is Set to Revolutionize Microscopy

Article Sources

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Before joining Discover Magazine, Paul Smaglik spent over 20 years as a science journalist, specializing in U.S. life science policy and global scientific career issues. He began his career in newspapers, but switched to scientific magazines. His work has appeared in publications including Science News, Science, Nature, and Scientific American.