RNA-Mediated Thermoregulation of Iron-Acquisition Genes in Shigella dysenteriae and Pathogenic Escherichia coli

• Published in: PloS one Vol. 8; no. 5; p. e63781
• Main Authors: Kouse, Andrew B., Righetti, Francesco, Kortmann, Jens, Narberhaus, Franz, Murphy, Erin R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.05.2013; Public Library of Science (PLoS)
• Subjects: 5' Untranslated Regions - genetics; Bacteria; Bacterial diseases; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; Biology; Body temperature; Computer Simulation; Diarrhea; Disease transmission; DNA Mutational Analysis; E coli; Environment; Environmental conditions; Environmental impact; Escherichia coli; Escherichia coli - genetics; Gene expression; Gene Expression Regulation, Bacterial; Gene regulation; Genes, Bacterial - genetics; Genes, Reporter; Green Fluorescent Proteins - metabolism; Heme; Humans; Infections; Iron; Iron - metabolism; Low temperature; Models, Biological; Molecular Sequence Data; Mutagenesis, Site-Directed; Nucleic Acid Conformation; Nucleic acids; Nucleotide sequence; Nutrient utilization; Nutrients; Pathogens; Post-transcription; Promoter Regions, Genetic - genetics; Protein Biosynthesis - genetics; Proteins; Ribonucleic acid; RNA; RNA, Bacterial - chemistry; RNA, Bacterial - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Salmonella; Shigella; Shigella dysenteriae; Shigella dysenteriae - genetics; Shigellosis; Structure-function relationships; Target recognition; Temperature; Temperature effects; Thermoregulation; Transcription, Genetic; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063781

The initiation, progression and transmission of most bacterial infections is dependent upon the ability of the invading pathogen to acquire iron from each of the varied environments encountered during the course of a natural infection. In total, 95% of iron within the human body is complexed within heme, making heme a potentially rich source of host-associated nutrient iron for invading bacteria. As heme is encountered only within the host, pathogenic bacteria often regulate synthesis of heme utilization factors such that production is maximal under host-associated environmental conditions. This study examines the regulated production of ShuA, an outer-membrane receptor required for the utilization of heme as a source of nutrient iron by Shigella dysenteriae, a pathogenic bacterium that causes severe diarrheal diseases in humans. Specifically, the impact of the distinct environmental temperatures encountered during infection within a host (37°C) and transmission between hosts (25°C) on shuA expression is investigated. We show that shuA expression is subject to temperature-dependent post-transcriptional regulation resulting in increased ShuA production at 37°C. The observed thermoregulation is mediated by nucleic acid sequences within the 5' untranslated region. In addition, we have identified similar nucleotide sequences within the 5' untranslated region of the orthologous chuA transcript of enteropathogenic E. coli and have demonstrated that it also functions to confer temperature-dependent post-transcriptional regulation. In both function and predicted structure, the regulatory element within the shuA and chuA 5' untranslated regions closely resembles a FourU RNA thermometer, a zipper-like RNA structure that occludes the Shine-Dalgarno sequence at low temperatures. Increased production of ShuA and ChuA in response to the host body temperature allows for maximal production of these heme acquisition factors within the environment where S. dysenteriae and pathogenic E. coli strains would encounter heme, a host-specific iron source.