Anaerobic Regulation of Shigella flexneri Virulence: ArcA Regulates fur and Iron Acquisition Genes

The University of Texas at Austin, Section .
Journal of Bacteriology (Impact Factor: 2.81). 11/2007; 189(19):6957-67. DOI: 10.1128/JB.00621-07
Source: PubMed


Invasion and plaque formation in epithelial monolayers are routinely used to assess the virulence of Shigella flexneri, a causative agent of dysentery. A modified plaque assay was developed to identify factors contributing to the virulence
of S. flexneri under the anaerobic conditions present in the colon. This assay demonstrated the importance of the ferrous iron transport
system Feo, as well as the global transcription factors Fur, ArcA, and Fnr, for Shigella plaque formation in anoxic environments. Transcriptional analyses of S. flexneri iron transport genes indicated that anaerobic conditions activated feoABC while repressing genes encoding two other iron transport systems, the ABC transporter Sit and the Iuc/Iut aerobactin siderophore
synthesis and transport system. The anaerobic transcription factors ArcA and Fnr activated expression of feoABC, while ArcA repressed iucABCD iutA. Transcription of fur, encoding the iron-responsive transcriptional repressor of bacterial iron acquisition, was also repressed anaerobically in
an ArcA-dependent manner.

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Available from: Shelley M Payne, Jul 16, 2014
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    • "Genome sequences are available for at least one representative species for more than 20 different genera of enterobacteria ( To our knowledge changes in global gene expression under oxygen limitation have been documented for only five of them (E. coli K-12 MG1655 [19]: Salmonella enterica serovar Typhimurium [20]:, Shigella [21]:, Dickeya dadantii 3937 and Pectobacterium atrosepticum SCRI1043 [22]:). Thus the range of metabolic responses to O2 and the mechanisms that govern them are still incompletely understood for this family of facultative anaerobes. "
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    ABSTRACT: The yersiniae (Enterobacteriaceae) occupy a variety of niches, including some in human and flea hosts. Metabolic adaptations of the yersiniae, which contribute to their success in these specialized environments, remain largely unknown. We report results of an investigation of the transcriptome under aerobic and anaerobic conditions for Y. intermedia, a non-pathogenic member of the genus that has been used as a research surrogate for Y. pestis. Y. intermedia shares characteristics of pathogenic yersiniae, but is not known to cause disease in humans. Oxygen restriction is an important environmental stimulus experienced by many bacteria during their life-cycles and greatly influences their survival in specific environments. How oxygen availability affects physiology in the yersiniae is of importance in their life cycles but has not been extensively characterized.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "In E. coli ArcB senses oxygen availability via the quinone redox status (Q/QH2 and menaquinone/menaquinol) and tunes aerobic and anaerobic respiratory metabolism through its phosphorylation of ArcA [42]. ArcA functions as a transcriptional regulator of operons involved in respiratory and fermentative metabolism; ArcA plays a role in virulence in a wide variety of pathogenic bacteria in animals and humans including the enteric pathogens Vibrio cholerae[43] and Shigella flexneri[44]. Mutations in genes encoding respiratory chain complexes also identify components in pathogens essential for virulence. Rat lung fibroblasts exposed to Shigella flexneri with mutations in the cytochrome bd oxidase had lower numbers of plaques than fibroblasts infected with the wild-type parental strain [45]. "
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    • "Typically, Fur acts as a transcriptional repressor by binding to regulatory Fur box sequences in the promoters of iron-regulated genes under iron-repleted conditions. This protein also acts as a global regulator controlling the expression of iron acquisition and storage genes as well as the expression of genes involved in the oxidative stress response, virulence genes and small, iron-repressible regulatory RNAs [42], [43], [44]. The activation of the gene azo0644, encoding the Fur protein, in conditioned supernatant would repress the expression of Fur-dependent genes in Azoarcus sp. "
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    Full-text · Article · Jan 2012 · PLoS ONE
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