Industrial hog operation (IHO) workers are at increased risk of carrying
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The Enhancer-Binding Protein MifR, an Essential Regulator of α-Ketoglutarate Transport, Is Required for Full Virulence of Pseudomonas aeruginosa PAO1 in a Mouse Model of Pneumonia
ABSTRACT The opportunistic human pathogen Pseudomonas aeruginosa PAO1 has an extensive metabolism, enabling it to utilize a wide range of structurally diverse compounds to meet its nutritional and energy needs. Interestingly, the utilization of some of the more unusual compounds often associated with a eukaryotic-host environment is regulated via enhancer-binding proteins (EBPs) in P. aeruginosa . Whether the utilization of such compounds and the EBPs involved contribute to the pathogenesis of P. aeruginosa remains to be fully understood. To narrow this gap, we investigated the roles of the EBPs EatR (regulator of ethanolamine catabolism), DdaR (regulator of methylarginine catabolism), and MifR (regulator of α-ketoglutarate or α-KG transport) in the virulence of P. aeruginosa PAO1 in a pneumonia-induced septic mouse model. Deletion of genes encoding EatR and DdaR had no significant effect on the mortality of P. aeruginosa PAO1-infected mice compared to wide-type (WT) PAO1-infected mice. In contrast, infected mice with Δ mifR mutant exhibited a significant reduction (~50%) in the mortality rate compared with WT PAO1 ( P < 0.05). Infected mice with Δ mifR PAO1 had lower lung injury scores, fewer inflammatory cells, decreased proinflammatory cytokines, and decreased apoptosis and cell death compared to mice infected with WT PAO1 more »
- Editors:
- Brodsky, Igor E.
- Award ID(s):
- 1722630
- Publication Date:
- NSF-PAR ID:
- 10388500
- Journal Name:
- Infection and Immunity
- Volume:
- 90
- Issue:
- 10
- ISSN:
- 0019-9567
- Sponsoring Org:
- National Science Foundation
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