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

Israeli researchers have discovered that administering antibiotics can fully reverse the damage caused by salmonella to stem cells in mice, offering promising implications for patients undergoing stem cell transplants. The study, conducted by a team at Ben-Gurion University of the Negev, demonstrated that treating infected mice with antibiotics restored their stem cells to healthy levels, potentially improving outcomes for individuals awaiting blood transplants. The research began with the creation of a novel mouse model designed to replicate the effects of chronic salmonella infections in humans. This model allowed scientists to observe how the infection impacts hematopoietic stem cells (HSCs), the rare population of cells responsible for producing all types of blood cells. In a healthy body, HSCs remain dormant, preserving their ability to generate new blood cells. However, during an infection, these cells become highly active, dividing continuously to produce inflammatory white blood cells. Over time, this relentless activity leads to exhaustion of the stem cells, significantly reducing their capacity for transplantation. Prof. Roi Gazit, who led the research at Ben-Gurion University, explained that the study revealed a critical insight: once antibiotic treatment was initiated, the mice not only recovered from the infection but also regained functional HSCs. This finding suggests that timely intervention could prevent irreversible damage to the stem cell population, thereby enhancing the success rates of stem cell transplants. Salmonella, a common foodborne pathogen, infects approximately one in ten people globally each year, according to the World Health Organization. While many cases resolve without complications, chronic infections can lead to systemic issues, including damage to vital organs and impaired immune function. In laboratory settings, standard mice often succumb to salmonella infections within days, limiting the ability to study long-term consequences. To address this challenge, the research team partnered with Professor Roy Curtiss III at Arizona State University, who developed a modified strain of salmonella that allows for prolonged observation of its effects. Using this advanced model, the team observed that mice infected with the modified salmonella experienced mild symptoms initially. After 14 days, however, the infection progressed to cause severe weight loss and massive enlargement of the spleen. Within the bone marrow, the HSCs showed a dramatic decline in functionality, losing nearly all their regenerative capacity. At this stage, the stem cells were essentially rendered unusable for transplantation. Graduate student Erez Elfassy played a key role in establishing the experimental conditions, ensuring that the mice remained viable for extended periods while maintaining accurate representation of human disease progression. The results of the study, published in Cell Reports, indicate that antibiotics not only halted the progression of the infection but also facilitated recovery of the damaged stem cells. Stem cell transplants are a crucial treatment for a variety of diseases, including leukemia, lymphoma, and certain genetic disorders. Globally, around 90,000 such procedures are performed annually, with Israel conducting approximately 500 per year. The Bone Marrow Registry at Ezer Mitzion maintains over 1.3 million potential donors, highlighting the significance of effective stem cell therapies. The ability to restore damaged HSCs through antibiotic treatment could revolutionize the field, particularly for patients whose stem cells have been compromised by infection or disease.