Superbugs Beware!
Staph infections are responsible for an increasing number of life threatening infections and the bacteria that cause these infections are widespread in the community and the healthcare system. The bacterium Staphylococcus aureus normally resides on skin and in noses and infects tissues through cuts or rashes. Humans that lack a molecule known as C/EBPε are missing an important bacteria-fighting component of their immune systems and are highly susceptible to bacterial infections, including staph. This week in the Journal of Clinical Investigation, Kyme et al. report that treatment with Vitamin B3 increased the expression of C/EBPε and promoted bacterial clearance in staph-infected mice. The images above depict staph infection in normal mice and mice lacking C/EBPε. News outlets, including the BBC, are also talking about the impact of this research on the treatment of Staphylococcus aureus.
Related articles
Abstract
The myeloid-specific transcription factor, CCAAT/enhancer-binding protein ε (C/EBPε) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPε-deficient mice are severely affected by infection with S. aureus, and C/EBPε deficiency in neutrophils contributes to the infectious phenotype. Conversely, exposure to the epigenetic modulator nicotinamide (vitamin B3) increased expression of C/EBPε in WT myeloid cells. Further, nicotinamide increased the activity of C/EBPε and select downstream antimicrobial targets, particularly in neutrophils. In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPε-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPε is an important target to boost killing of bacteria by the innate immune system.
Authors
Pierre Kyme, Nils H. Thoennissen, Ching Wen Tseng, Gabriela B. Thoennissen, Andrea J. Wolf, Kenichi Shimada, Utz O. Krug, Kunik Lee, Carsten Müller-Tidow, Wolfgang E. Berdel, W. David Hardy, Adrian F. Gombart, H. Phillip Koeffler, George Y. Liu
Copyright © 2024 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)