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Direct Regulons of AtxA, the Master Virulence Regulator of Bacillus anthracis

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Title: Direct Regulons of AtxA, the Master Virulence Regulator of Bacillus anthracis
Authors: Furuta, Yoshikazu Browse this author
Cheng, Cheng Browse this author
Zorigt, Tuvshinzaya Browse this author
Paudel, Atmika Browse this author →KAKEN DB
Izumi, Shun Browse this author
Tsujinouchi, Mai Browse this author
Shimizu, Tomoko Browse this author
Meijer, Wim G. Browse this author
Higashi, Hideaki Browse this author →KAKEN DB
Keywords: Bacillus anthracis
DNA-binding proteins
small RNA
transcription factors
transcriptional regulation
virulence factors
Issue Date: 20-Jul-2021
Publisher: American Society for Microbiology
Journal Title: Msystems
Volume: 6
Issue: 4
Start Page: e00291-21
Publisher DOI: 10.1128/mSystems.00291-21
Abstract: AtxA, the master virulence regulator of Bacillus anthracis, regulates the expression of three toxins and genes for capsule formation that are required for the pathogenicity of B. anthracis. Recent transcriptome analyses showed that AtxA affects a large number of genes on the chromosome and plasmids, suggesting a role as a global regulator. However, information on genes directly regulated by AtxA is scarce. In this work, we conducted genome-wide analyses and cataloged the binding sites of AtxA in vivo and transcription start sites on the B. anthracis genome. By integrating these results, we detected eight genes as direct regulons of AtxA. These consisted of five protein-coding genes, including two of the three toxin genes, and three genes encoding the small RNAs XrrA and XrrB and a newly discovered 95-nucleotide small RNA, XrrC. Transcriptomes from single-knockout mutants of these small RNAs revealed changes in the transcription levels of genes related to the aerobic electron transport chain, heme biosynthesis, and amino acid metabolism, suggesting their function for the control of cell physiology. These results reveal the first layer of the gene regulatory network for the pathogenicity of B. anthracis and provide a data set for the further study of the genomics and genetics of B. anthracis. IMPORTANCE Bacillus anthracis is the Gram-positive bacterial species that causes anthrax. Anthrax is still prevalent in countries mainly in Asia and Africa, where it causes economic damage and remains a public health issue. The mechanism of pathogenicity is mainly explained by the three toxin proteins expressed from the pXO1 plasmid and by proteins involved in capsule formation expressed from the pXO2 plasmid. AtxA is a protein expressed from the pXO1 plasmid that is known to upregulate genes involved in toxin production and capsule formation and is thus considered the master virulence regulator of B. anthracis. Therefore, understanding the detailed mechanism of gene regulation is important for the control of anthrax. The significance of this work lies in the identification of genes that are directly regulated by AtxA via genome-wide analyses. The results reveal the first layer of the gene regulatory network for the pathogenicity of B. anthracis and provide useful resources for a further understanding of B. anthracis.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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