The bacterium Acinetobacter baumannii is causing an increasing number of infections in the hospital setting – and most strains are resistant to commonly used antibiotics. To identify new therapeutic approaches to combat this pathogen, Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Chair in Pathology, and colleagues explored the role of nutrient metals in A. baumannii infections.
The researchers found that calprotectin, a host protein that binds metals and has antimicrobial activity, inhibits A. baumannii growth in vitro by binding manganese and zinc. They showed that calprotectin accumulates in the mouse lung following an infectious challenge and protects against A. baumannii pneumonia and dissemination of the bacteria to other organs.
Using calprotectin as a probe, the researchers discovered A. baumannii’s zinc acquisition system and found that this system is required for full bacterial pathogenesis. They also demonstrated that limiting zinc availability reversed the antibiotic resistance of a carbapenem-resistant strain of A. baumannii.
The findings, reported in the December PLOS Pathogens, establish zinc acquisition as a therapeutic target for fighting A. baumannii infections.
This research was supported by grants from the National Institutes of Health (AI091771, GM103391) and by an investigator award from the Burroughs Wellcome Fund.
