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Nashville, Tenn. — A groundbreaking study published on November 15 in Nature Microbiology reveals that dietary zinc deficiency can exacerbate lung infections caused by Acinetobacter baumannii, a major pathogen responsible for ventilator-associated pneumonia. The research, led by a Vanderbilt University Medical Center (VUMC) team, highlights a novel treatment avenue involving anti-inflammatory therapies.
The study uncovers a surprising connection between zinc deficiency, the pro-inflammatory cytokine interleukin-13 (IL-13), and the severity of A. baumannii infections. Researchers demonstrated that blocking IL-13 could prevent infection-associated deaths in animal models. These findings raise the potential of using FDA-approved anti-IL-13 antibodies to treat bacterial pneumonia in zinc-deficient patients.
“This is the first study showing that neutralization of IL-13 could prevent mortality from a bacterial infection,” said Dr. Eric Skaar, the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology, and Inflammation. “It suggests anti-IL-13 therapy as part of a personalized approach for patients with zinc deficiency and A. baumannii pneumonia.”
Zinc Deficiency and Public Health Risks
Nearly 20% of the global population faces zinc deficiency, a condition that impairs immune function and is a significant risk factor for pneumonia, according to the World Health Organization. Critically ill and elderly patients, especially those in health care settings, are particularly vulnerable.
Patients on ventilators or with prolonged hospital stays are at the highest risk of contracting A. baumannii, which is increasingly resistant to antibiotics and considered a serious public health threat.
The Role of Zinc in Combating A. baumannii
To investigate zinc deficiency’s role in worsening A. baumannii infections, researchers developed a mouse model of dietary zinc deficiency and acute bacterial pneumonia. The study, led by Dr. Lauren Palmer, now an assistant professor at the University of Illinois, Chicago, revealed stark differences in outcomes between zinc-deficient and zinc-sufficient mice.
Zinc-deficient mice exhibited higher bacterial loads in their lungs, the spread of infection to the spleen, and increased mortality rates. Elevated IL-13 production was identified as a critical factor, as it exacerbated bacterial spread and worsened outcomes. Conversely, administering anti-IL-13 antibodies significantly improved survival rates in zinc-deficient mice.
“These findings suggest that IL-13 may be a critical risk factor for health care-associated lung infections,” noted Skaar.
Therapeutic Implications
Anti-IL-13 therapies, such as lebrikizumab and tralokinumab, have been tested in clinical trials for severe asthma. Although they were not effective for asthma, the trials demonstrated their safety, suggesting their potential repurposing for combating bacterial infections in zinc-deficient individuals.
The study was a collaborative effort involving VUMC and researchers from other institutions, supported by funding from the National Institutes of Health.
“This work opens new possibilities for personalized treatments targeting nutrient deficiencies and immune responses in high-risk patients,” said Palmer, co-corresponding author of the study.
With antimicrobial resistance on the rise, the findings offer a beacon of hope for managing deadly infections in vulnerable populations.
