Israeli study finds antibiotics can reverse salmonella damage to stem cells in mice

Reporter at The Times of Israel

Damage to stem cells caused by salmonella, a chronic bacterial infection affecting millions worldwide, can be completely reversed in mice that are treated with antibiotics, Israeli scientists say.

Using a breakthrough mouse model, a team of researchers at Ben-Gurion University of the Negev replicated how the chronic illness generally acts in humans.

The researchers found that once antibiotics were administered, the mice not only recovered, but their stem cells also returned to healthy levels.

“The experiment gives hope to people waiting for blood transplants and waiting for donors to get better,” Prof. Roi Gazit, who heads a stem cell laboratory at Ben-Gurion University and supervised the research, told The Times of Israel in a video call.

“Now that we have the model,” Gazit said, “we can gain more knowledge, and maybe we can improve bone marrow transplant as a whole.”

Gazit said the findings of the study, which was published in Cell Reports, are “very optimistic.”

Around the world, about 90,000 stem cell transplants are done each year, according to the Worldwide Network for Blood and Marrow Transplantation.

In Israel, about 500 transplants are performed annually. The Bone Marrow Registry at Ezer Mitzion includes more than 1.3 million potential donors to help people struggling with leukemia, lymphoma, and other cancers. Stem cell transplants completely rebuild a patient’s blood and immune systems.

“People know that humans make new blood cells every day, every second throughout life,” Gazit said. “The rate is mind-blowing. It’s more than 1 million new blood cells every second. Even when you’re sitting, your bone marrow produces an astronomical number of new blood cells, and that’s merely to keep normal life in balance.”

However, the system of blood production relies on a minuscule, rare population of cells known as hematopoietic stem cells (HSCs) that reside in the bone marrow. These cells are the ultimate source of all red blood cells, white blood cells, and platelets.

When the body is healthy, these HSCs “rest and keep their potency by not proliferating,” Gazit said.

But when the body has an infection, the stem cells go into “an emergency, hyperactive state of constant division to churn out inflammatory white blood cells to fight the bacteria,” Gazit said.

The stem cells quickly exhaust themselves, Gazit said, and their ability to be transplanted in another “drops to nearly zero.”

Although scientists have been aware of the impact of a chronic bacterial illness on these HSCs, studying these diseased stem cells is challenging, Gazit said, because they are constantly changing.

Gazit’s team focused on adult stem cells infected by salmonella, a common foodborne bacterium. According to the World Health Organization, it affects one in 10 people each year.

The disease is usually characterized by an acute onset of fever, abdominal pain, diarrhea, nausea, and sometimes vomiting. Gazit said that standard laboratory mice typically experience salmonella as an acute, rapidly fatal illness, making long-term observation impossible.

To overcome this hurdle, Gazit said the BGU lab collaborated with Arizona State University’s Prof. Roy Curtiss III, who provided a specialized, modified strain of salmonella.

BGU graduate student Erez Elfassy then established the lab model.

The mice became mildly ill. After 14 days, the infection caused severe weight loss and massively enlarged spleens.

In the mice’s bone marrow, the stem cells lost almost all their biological potency. They were pumping out inflammatory white blood cells at the expense of a healthy blood supply, and they were “flooded with signals linked to cellular distress,” Gazit explained.

Then, Elfassy, “because he’s a smart student,” Gazit said, treated the mice with antibiotics.

The mice recovered quickly, with their weight returning to normal and their enlarged spleens shrinking back to their proper size.

The team then partnered with the laboratory of Dr. Ofir Cohen at BGU to utilize single-cell RNA sequencing, a technology Gazit likened to a “very fancy microscope,” to determine how the infection affected the stem cells.

“The genetic mapping confirmed that the antibiotics calmed down the hyperactive, exhausted stem cells,” Gazit said. “The mice completely recovered, and the potency of their stem cells to transplant also recovered.”

“That’s the basic science,” Gazit explained. “Let’s say I need a bone marrow transplant. My brother, who is a match for transplantation, is willing to donate, but he’s sick today. Our answer is simple: give him antibiotics and let him rest, and his stem cells will recover.”

“My take-home message from this study is that it showcases the power of single-cell technologies to uncover how chronic inflammation reshapes HSCs at the molecular level,” Prof. Michael Milyavsky, a Tel Aviv University pathologist, told The Times of Israel.

Milyavsky was not involved in the research.

He said that beyond the biological insights, the work has “important translational implications,” suggesting that the inflammatory status of bone marrow donors “may be an important factor to consider before stem cell transplantation.”

“This raises the possibility that restoring stem cell fitness before transplantation could improve clinical outcomes,” he said. “While these findings still need to be validated in humans, they open an exciting avenue for developing strategies to optimize bone marrow transplantation.”

Gazit said that medical centers do not “really encourage” bone marrow transplant to people over 70 because it is a “formidable” procedure for people with other existing medical conditions.

“But many people today live past their 70s,” he said. “If we better understand the basic principles, we can suggest ways to allow bone marrow transplants in people who don’t get it today. This might save the lives of many people throughout Israel.”

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