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Addiction systems antagonize bacterial adaptive immunity.

Lisa van Sluijs1, Stineke van Houte2, John van der Oost1

  • 1Laboratory of Microbiology, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands.

FEMS Microbiology Letters
|March 6, 2019
PubMed
Summary

CRISPR-Cas immunity in bacteria does not provide a fitness benefit against conjugative plasmids without antibiotics. Toxin-anti-toxin systems on plasmids prevent CRISPR-Cas defenses from limiting antibiotic resistance spread.

Keywords:
CRISPRTAadaptive immunitybacteriaplasmidtoxin

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Area of Science:

  • Microbiology
  • Bacterial Genetics
  • Molecular Biology

Background:

  • CRISPR-Cas systems offer adaptive immunity against mobile genetic elements in bacteria.
  • However, CRISPR-Cas deployment often incurs a fitness cost for the host bacterium.
  • The role of CRISPR-Cas in preventing horizontal gene transfer of conjugative plasmids, crucial for antibiotic resistance spread, is unclear due to these costs and benefits.

Purpose of the Study:

  • To quantify the fitness costs and benefits of CRISPR-Cas mediated plasmid immunity.
  • To investigate the impact of plasmid addiction systems on CRISPR-Cas effectiveness.
  • To assess the implications for CRISPR-Cas systems in controlling antibiotic resistance dissemination.

Main Methods:

  • Utilized Escherichia coli and the conjugative plasmid pOX38-Cm to measure bacterial fitness.
  • Assessed fitness costs associated with CRISPR-Cas mediated plasmid immunity.
  • Investigated the influence of the CcdAB toxin-anti-toxin (TA) addiction system on plasmid carriage and CRISPR-Cas efficacy.

Main Results:

  • CRISPR-mediated immunity did not confer a fitness benefit in the absence of antibiotics, despite significant fitness costs of plasmid carriage.
  • The conjugative plasmid pOX38-Cm possesses a CcdAB toxin-anti-toxin (TA) addiction system.
  • The TA system's expression prior to plasmid detection and degradation by CRISPR-Cas negates the fitness benefit of CRISPR-mediated defense.

Conclusions:

  • CRISPR-Cas systems may not effectively limit the spread of conjugative plasmids carrying toxin-anti-toxin systems without antibiotic selection.
  • The prevalence of TA systems on antibiotic resistance plasmids could diminish the role of CRISPR-Cas in controlling their horizontal spread.
  • Understanding these interactions is critical for evaluating CRISPR-Cas as a strategy against antibiotic resistance.