Nucleotide Second Messengers Signal Through Transcriptional and Posttranscriptional Regulators to Control the Production of a Colonization Factor in Vibrio cholerae Public Deposited

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  • March 19, 2019
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  • Kariisa, Ankunda
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • The diarrheal human pathogen Vibrio cholerae causes millions of cases of severe cholera disease every year, resulting in substantial morbidity and mortality. Although V. cholerae is primarily an aquatic organism, it is also adept at colonizing and flourishing in the human small intestine. To persist and transition between the aquatic environment and the host, V. cholerae controls the production of colonization factors and virulence determinants. V. cholerae alters this through the production of intracellular second messengers, such as cyclic diguanylate (c-di-GMP) and cyclic adenosine monophosphate (cAMP), that relay information about the extracellular environment to intracellular effectors. Within the cell, c-di-GMP interacts with a variety of effector molecules, such as RNA riboswitches and proteins, to achieve transcriptional, post-transcriptional and post-translational control of regulated processes. cAMP signals primarily through its receptor, the cAMP Receptor Protein (CRP), and regulates processes at the level of transcription. In this study, we examine the regulation of gbpA by c-di-GMP and cAMP; GbpA is a colonization factor that contributes to attachment of V. cholerae to the host small intestine and to chitinous surfaces. A c-di-GMP riboswitch, Vc1, was recently identified in the 5’ untranslated region of gbpA. Our results show that Vc1 can bind c-di-GMP in vitro and that mutations that reduce binding abrogate GbpA production. Thus, c-di-GMP positively regulates gbpA expression via Vc1. In addition, we defined an additional mechanism of regulation of gbpA in which c-di-GMP negatively impacts activation gbpA transcription initiation by acting through cAMP-CRP. These studies identify two distinct signals, c-di-GMP and cAMP, that contribute to the regulation of gbpA. Our findings highlight the complex contribution of nucleotide second messengers in the adaptation of V. cholerae to host and aquatic environments.
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  • In Copyright
Advisor
  • Richardson, Anthony
  • Wolfgang, Matthew
  • Tamayo, Rita
  • Miller, Virginia
  • Cotter, Peggy
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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