Comparative transcriptomics and genomics from continuous axenic media growth identifies Coxiella burnetii intracellular survival strategies.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 101595366 Publication Model: Print Cited Medium: Internet ISSN: 2049-632X (Electronic) Linking ISSN: 2049632X NLM ISO Abbreviation: Pathog Dis Subsets: MEDLINE
    • Publication Information:
      Publication: 2015- : Oxford Oxford University Press
      Original Publication: [Malden, MA] : Wiley-Blackwell, [2013]-
    • Subject Terms:
      Coxiella burnetii* ; Q Fever*; Humans ; Transcriptome ; Gene Expression Profiling ; Genomics
    • Abstract:
      Coxiella burnetii (Cb) is an obligate intracellular pathogen in nature and the causative agent of acute Q fever as well as chronic diseases. In an effort to identify genes and proteins crucial to their normal intracellular growth lifestyle, we applied a 'reverse evolution' approach where the avirulent Nine Mile Phase II strain of Cb was grown for 67 passages in chemically defined ACCM-D media and gene expression patterns and genome integrity from various passages was compared to passage number one following intracellular growth. Transcriptomic analysis identified a marked downregulation of the structural components of the type 4B secretion system (T4BSS), the general secretory (Sec) pathway, as well as 14 out of 118 previously identified genes encoding effector proteins. Additional downregulated pathogenicity determinants genes included several chaperones, LPS, and peptidoglycan biosynthesis. A general marked downregulation of central metabolic pathways was also observed, which was balanced by a marked upregulation of genes encoding transporters. This pattern reflected the richness of the media and diminishing anabolic, and ATP-generation needs. Finally, genomic sequencing and comparative genomic analysis demonstrated an extremely low level of mutation across passages, despite the observed Cb gene expression changes following acclimation to axenic media.
      (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)
    • Comments:
      Update of: bioRxiv. 2023 Feb 06:2023.02.06.527305. doi: 10.1101/2023.02.06.527305. (PMID: 36798183)
    • Grant Information:
      R03 AI149144 United States AI NIAID NIH HHS; United States NH NIH HHS
    • Contributed Indexing:
      Keywords: Coxiella burnetii; effector proteins; intracellular survival; reverse evolution; type 4B secretion system
    • Publication Date:
      Date Created: 20230516 Date Completed: 20230615 Latest Revision: 20240517
    • Publication Date:
      20250114
    • Accession Number:
      PMC10237335
    • Accession Number:
      10.1093/femspd/ftad009
    • Accession Number:
      37193663