Thus, these two global regulators may be directly involved in reg

Thus, these two global regulators may be directly involved in regulation of these 12 genes (Additional BVD-523 file 4: Table S4). The expression data

Crenigacestat clinical trial indicated that Fur and Fnr cooperate in the regulation of these 12 genes. For instance, each gene was regulated in the same manner in Δfur or Δfnr; a gene activated by Fur was also activated by Fnr. Lastly, our investigations indicate that Fur indirectly regulates genes that are under control of Fnr or additional regulators with an iron sulfur cluster (i.e., ftnB and hmpA). Furthermore, the observed reduced expression of the ethanolamine operon, frdABD, and dmsABC in Δfur, suggest altered regulation of operons induced under anaerobiosis (Additional file 2: Table S2). Thus, Fur is an activator of genes that are typically induced under anaerobic conditions. Ethanolamine utilization within the host is important for S. Typhimurium and the Gram-positive pathogen Listeria monocytogenes [118, 119]. In addition, Fnr is an activator of the frd and dms operons, which are responsible for anaerobic utilization of fumarate and dimethyl sulfide as alternative electron acceptors, respectively [120–123]. Our study of the anaerobic expression of hmpA suggests that it is regulated by Fur, independent of Fnr. Clearly,

Selleckchem GSK2879552 these results suggest Fnr is functional in Δfur and that Fur is regulating genes of anaerobic metabolism (eut, frd, and dms operons) through an unknown mechanism. Conclusions We demonstrated that Fur is an activator of ftnB in S. Typhimurium, which is likely due to the de-repression of hns in Δfur. The strong dependence of ftnB expression on O2 indicates that Fnr is crucial in its regulation. Additionally, we presented evidence that Fur indirectly controls hmpA, independent of Fnr. We determined that Fur represses sodA transcription, but is required for the maturation of SodA into an active enzyme, MnSOD. Finally, we identified new target genes regulated by Fur in S. Typhimurium, and our data support the increasing evidence of enhanced H-NS expression in Δfur. Acknowledgements and Funding This work was supported in part

by the North Carolina Agricultural Research Service (to HMH. BT was supported, in part, by NIH T32 AI060519. MM and SP were supported in part by NIH grants R01AI 083646, R01AI 075093, R21AI 083964, Beta adrenergic receptor kinase R01AI 07397, R01AI 039557 and R01AI 052237. We are grateful to Drs. FC Fang, SJ Libby, and A Vazquez-Torres for strains and plasmids. We thank Gabriele Gusmini and Russell Wolfinger for guidance with statistical analysis; and Fred Long and Xiao-Qin Xia for their expert bioinformatics assistance. We thank Dr. M. Evans for reading the manuscript and Dr. Robarge and Kim Hutchison for ICP-OES analysis of metals. Electronic supplementary material Additional file 1: Table S1. Primer table. This file contains the sequence of primers used in this study. (PDF 86 KB) Additional file 2: Table S2. Fur Regulated Genes.

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