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Degeneration of a CRISPR/Cas system and its regulatory target during the evolution of a pathogen

Timothy R Sampson1, David S Weiss2

  • 1Department of Microbiology and Immunology, Microbiology and Molecular Genetics Program; Emory University School of Medicine; Atlanta, GA USA; Emory Vaccine Center; Emory University School of Medicine; Atlanta, GA USA; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA.

RNA Biology
|October 9, 2013
PubMed

Insights

CRISPR/Cas systems regulate gene expression and virulence in bacteria. Degenerated CRISPR/Cas systems in Francisella species correlate with enhanced virulence, suggesting loss of this system permits genome alterations and adaptations.

Area of Science:

  • Bacteriology
  • Genetics
  • Molecular Biology

Background:

  • CRISPR/Cas systems are prokaryotic adaptive immune systems targeting foreign nucleic acids.
  • Cas9 protein in Francisella novicida regulates gene expression and virulence by controlling mRNA stability.
  • Francisella species with higher virulence exhibit degenerated CRISPR/Cas systems.

Purpose of the Study:

  • To investigate the role of CRISPR/Cas system degeneration in bacterial virulence.
  • To understand the evolutionary implications of CRISPR/Cas loss in Francisella.

Main Methods:

  • Genomic analysis of Francisella species.
  • mRNA stability assays.
  • Gene expression analysis.

Main Results:

  • Degenerated CRISPR/Cas systems were identified in highly virulent Francisella species.
  • Loss of CRISPR/Cas function appears to remove a barrier to genome alteration, enhancing virulence.
  • The bacterial lipoprotein (BLP) locus was lost in these virulent strains, likely due to adaptation to the absence of Cas9-mediated repression.

Conclusions:

  • CRISPR/Cas degeneration can lead to enhanced bacterial virulence through genomic alterations.
  • Loss of CRISPR/Cas systems may necessitate compensatory genomic changes for bacterial fitness.
  • These findings highlight the regulatory roles of CRISPR/Cas systems and their evolutionary impact.
Keywords:
CRISPR/Casbacterial evolutionbacterial pathogenesisgene expressionregulatory RNA

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