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Late-Exponential Gene Expression in codY-Deficient Bacillus anthracis in a Host-Like Environment

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Abstract

CodY is a pleiotropic regulator commonly found in Gram-positive bacteria and regulates various biological processes during the stringent response in a nutrient-limiting environment. CodY also participates in virulence factor expression in many low G+C Gram-positive pathogens, as observed in Bacillus anthracis. However, the mechanism by which B. anthracis CodY regulates metabolism and virulence factors in response to environmental changes is unclear. Here, we attempted to identify the link between CodY and B. anthracis regulation with codY-deficient and codY-overexpressing mutants using high-throughput transcriptional analysis. Growth pattern analyses of codY mutants in both rich and minimal media showed defects in early cell proliferation, with opposite patterns in the early stationary phase: CodY overexpression prolonged bacterial growth, whereas deletion inhibited growth. RNA sequencing of codY-deficient B. anthracis showed both positive and negative changes in the gene expression of proteases and virulence factors as well as genes related to stringent response-related metabolism and biosynthetic processing. We also found that changes in codY expression could alter virulence gene expression of B. anthracis, suggesting modes of regulation in its virulence in a CodY concentration-dependent manner. Collectively, we conclude from these results that CodY can both positively and negatively regulate its regulon via direct and/or indirect approaches, and that its mode of regulation may be concentration dependent.

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Acknowledgments

We thank Dr. Konstantin Shatalin for providing an integration vector pKS1, and Dr. Abraham Sonenshein for anti-CodY antibody. This research was supported by Global Ph. D. Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012-003722), NRF Grant funded by Korean Government (MSIP 2011-0030049) and Agency of Defense Development (UC13002320).

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Authors and Affiliations

  1. Department of Molecular and Life Science, Hanyang University, 1271, Ansan, Gyeonggi-do, 15588, Republic of Korea

    Se Kye Kim, Kyoung Hwa Jung & Young Gyu Chai

  2. Samyang Chemical Co., Ltd, Seoul, Republic of Korea

    Sung Nyo Yoon & Yun Ki Kim

  3. Department of Bionanotechnology, Hanyang University, Seoul, Republic of Korea

    Young Gyu Chai

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  1. Se Kye Kim
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Correspondence to Young Gyu Chai.

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Kim, S.K., Jung, K.H., Yoon, S.N. et al. Late-Exponential Gene Expression in codY-Deficient Bacillus anthracis in a Host-Like Environment. Curr Microbiol 73, 714–720 (2016). https://doi.org/10.1007/s00284-016-1120-y

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  • DOI: https://doi.org/10.1007/s00284-016-1120-y

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