JB Accepts, published online ahead of print on 23 October 2009

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J. Bacteriol. doi:10.1128/JB.00741-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Transcriptional and Functional Analysis of the Neisseria gonorrhoeae Fur Regulon

Lydgia A. Jackson^*, Thomas F. Ducey, Michael W. Day, Jeremy B. Zaitshik, Joshua Orvis, and David W. Dyer

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Agricultural Research Service, Florence, SC; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD

^* To whom correspondence should be addressed. Email: lydgia-jackson{at}ouhsc.edu.

To ensure survival in the host, bacteria have evolved strategies to acquire the essential element iron. In Neisseria gonorrhoeae, the ferric uptake regulator Fur regulates metabolism through transcriptional control of iron-responsive genes by binding conserved Fur box (FB) sequences in promoters during iron-replete growth. Our previous studies showed Fur also controls transcription of secondary regulators that in turn may control pathways important to pathogenesis, indicating an indirect role for Fur in controlling these downstream genes. To better define the iron-regulated cascade of transcriptional control, we combined three global strategies: temporal transcriptome analysis, genome-wide in silico FB prediction, and FuRTA assays to detect genomic regions able to bind Fur in vivo. The majority of the 300 iron-repressed genes were predicted to be of unknown function, followed by genes involved in iron metabolism, cell communication, and intermediary metabolism. The 107 iron-induced genes encoded hypothetical proteins or energy metabolism functions. We found 28 predicted FB in FuRTA positive clones in promoters and within open reading frames of iron-repressed genes. We found decreased conservation at critical thymidine residues involved in Fur binding in the FB sequence logo of FuRTA positive clones with intragenic FB compared to the sequence logo generated from FuRTA positive promoter regions. In EMSA studies, intragenic FB bound Fur at a lower affinity compared to intergenic FB. Our findings further indicate that transcription under iron stress is being indirectly controlled by Fur through twelve potential secondary regulators.