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This is why some patients suffer a relapse after antibiotic therapy

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A new study answers: why antibiotic therapy fails to kill Salmonella and how every 100th bacterium survives

Antibiotics are effective against a wide range of bacterial infections. Some patients, however, experience a relapse. A team of researchers from the University of Basel has figured out why some bacteria may withstand the antibiotic treatment. The researchers revealed where bacteria hide in the body and how the body’s own immune system is involved.

Infections caused by bacteria, such as tuberculosis or typhoid fever, are usually treatable with antibiotics, as long as the bacteria are not resistant. However, complete eradication of bacteria is not always possible. A few viruses can survive antibiotic treatment and induce relapse in some patients. Scientists have been attempting to figure out why antibiotics don’t kill all bacteria for a long time.

Professor Dirk Bumann’s team at the Biozentrum at the University of Basel has now demonstrated that it is not due to dormant and thus insensitive infections, as one might anticipate. Rather, the typhoid fever-causing Salmonella can live in some parts of the tissue, mostly undisturbed by the body’s immunological systems.

The findings were reported in the journal PNAS.

“After antibiotic therapy, only about every 100th bacterium survives,” said study lead author Dirk Bumann.

“Tracking down and studying these few Salmonella in tissues is like looking for the needle in the haystack.”

The researchers used serial two-photon tomography, a tool used before in neurobiology to detect the tiniest nerve fibers in the brain, to complete this Sisyphean task. The scanner captures an image of the tissue surface before removing the top layer. The fresh surface is scanned once again before the next cut is made. As a result, the tool slices its way through the tissue, slice by slice. This gives the researchers a precise three-dimensional image of the tissue and indicates the location of the few surviving bacteria.

Salmonella survives antibiotic therapy in the white pulp (red) of the spleen.

The researchers imaged the spleens of infected mice in their investigation. The majority of Salmonella dwell in the spleen’s red pulp, which serves as a red blood cell recycling station.

“Here, Salmonella are almost totally eliminated during antibiotic treatment,” explained Jiagui Li, one of the first authors of the study.

Some Salmonella can also be found in the white pulp of the spleen, which is where immune responses are generally begun. Antibiotic therapy, on the other hand, is unsuccessful in this area. As a result, the white pulp becomes the primary habitat for surviving Salmonella.

“It’s ironic, that pathogens hide in the body exactly where they should be caught as the culprit and an effective defense against them should be activated,” said Bumann.

Antibiotics alone are insufficient.

How do the bacteria manage to survive in such an unusual environment? Antibiotics alone cannot eliminate Salmonella from tissue, according to the researchers, who discovered that the immune system is required to clear all pathogens. Neutrophils, which are white blood cells that successfully combat bacteria, are particularly important.

For Salmonella eradication to be successful, neutrophils must collaborate with the antibiotic for several days. However, there are few neutrophils in the white pulp, and their numbers plummet following treatment. With host neutrophil support dwindling, the antibiotic alone will not be able to eradicate the local Salmonella.

To address this issue, the research team attempted to strengthen the body’s defenses while also administering an immunological treatment.

“This approach can help to stimulate the immune system and to maintain a high density of neutrophils over a longer time,” added Bumann.

Indeed, adjunct therapy may result in more effective bacterial clearance, offering up new paths for preventing relapses.

Source: 10.1073/pnas.2113951118

Image Credit: Getty

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