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Characterization of the Neisseria gonorrhoeae Iron and Fur Regulatory Network.

Research paper by Chunxiao C Yu, Ryan R McClure, Kathleen K Nudel, Nadine N Daou, Caroline Attardo CA Genco

Indexed on: 02 Jun '16Published on: 02 Jun '16Published in: Journal of bacteriology



Abstract

The Neisseria gonorrhoeae Ferric Uptake Regulatory protein, Fur, controls expression of iron homeostasis genes in response to intracellular iron levels. In this study, using RNA-seq analysis of a N. gonorrhoeae fur strain we defined the gonococcal Fur and iron regulons and characterized Fur-controlled expression of an ArsR-like DNA binding protein. We observed that 158 genes (8% of the genome) showed differential expression in response to iron in a N. gonorrhoeae wild-type or fur strain while a 54 genes exhibited differential expression in response to Fur. The Fur regulon was extended to additional regulators including 13 sRNAs and NrrF, and two transcriptional factors. One transcriptional factor, coding for an ArsR-like regulator (ArsR), exhibited increased expression under iron-replete conditions in the wild-type strain, but showed decreased expression across iron conditions in the fur strain, an effect that was reversed in a fur complemented strain. Fur was shown to bind to the promoter region of the arsR gene downstream of a predicted σ70 promoter region. EMSA analysis confirmed binding of the ArsR protein to the norB promoter region and sequence analysis identified two additional putative targets, NGO1411 and NGO1646. A gonococcal arsR strain demonstrated decreased survival in human endocervical epithelial cells compared to the wild-type and arsR complemented strains, suggesting that the ArsR regulon includes genes required for survival in host cells. Collectively, these results demonstrate that the N. gonorrhoeae Fur functions as a global regulatory protein to repress or activate expression of a large repertoire of genes including additional transcriptional regulatory proteins.Gene regulation in bacteria in response to environmental stimuli, including iron, is of paramount importance to both bacterial replication and, in the case of pathogenic bacteria, successful infection. Bacterial DNA binding proteins are a common mechanism utilized by pathogens to control gene expression under various environmental conditions. Here, we show that the DNA binding protein Fur, expressed by the human pathogen Neisseria gonorrhoeae, controls the expression of a large repertoire of genes and extends this regulon by controlling expression of additional DNA-binding proteins. One of these proteins, an arsR-like regulator, was required for N. gonorrhoeae survival within host cells. These results show that the Fur regulon extends to additional regulatory proteins, which together contribute to gonococcal mechanisms of pathogenesis.