Addiction systems antagonize bacterial adaptive immunity

Lisa van Sluijs, Stineke van Houte, John van der Oost, Stan J.J. Brouns, Angus Buckling, Edze R. Westra

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

CRISPR-Cas systems provide adaptive immunity against mobile genetic elements, but employment of this resistance mechanism is often reported with a fitness cost for the host. Whether or not CRISPR-Cas systems are important barriers for the horizontal spread of conjugative plasmids, which play a crucial role in the spread of antibiotic resistance, will depend on the fitness costs of employing CRISPR-based defences and the benefits of resisting conjugative plasmids. To estimate these costs and benefits we measured bacterial fitness associated with plasmid immunity using Escherichia coli and the conjugative plasmid pOX38-Cm. We find that CRISPR-mediated immunity fails to confer a fitness benefit in the absence of antibiotics, despite the large fitness cost associated with carrying the plasmid in this context. Similar to many other conjugative plasmids, pOX38-Cm carries a CcdAB toxin-anti-toxin (TA) addiction system. These addiction systems encode long-lived toxins and short-lived anti-toxins, resulting in toxic effects following the loss of the TA genes from the bacterial host. Our data suggest that the lack of a fitness benefit associated with CRISPR-mediated defence is due to expression of the TA system before plasmid detection and degradation. As most antibiotic resistance plasmids encode TA systems this could have important consequences for the role of CRISPR-Cas systems in limiting the spread of antibiotic resistance.

LanguageEnglish
Article numberfnz047
JournalFEMS Microbiology Letters
Volume366
Issue number5
DOIs
Publication statusPublished - 1 Mar 2019

Fingerprint

Adaptive Immunity
Plasmids
CRISPR-Cas Systems
Clustered Regularly Interspaced Short Palindromic Repeats
Microbial Drug Resistance
Costs and Cost Analysis
Immunity
Interspersed Repetitive Sequences
Bacterial Toxins
Bacterial Genes
Poisons
Cost-Benefit Analysis
Escherichia coli
Anti-Bacterial Agents

Keywords

  • adaptive immunity
  • bacteria
  • CRISPR
  • plasmid
  • TA
  • toxin

Cite this

van Sluijs, Lisa ; van Houte, Stineke ; van der Oost, John ; Brouns, Stan J.J. ; Buckling, Angus ; Westra, Edze R. / Addiction systems antagonize bacterial adaptive immunity. In: FEMS Microbiology Letters. 2019 ; Vol. 366, No. 5.
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Addiction systems antagonize bacterial adaptive immunity. / van Sluijs, Lisa; van Houte, Stineke; van der Oost, John; Brouns, Stan J.J.; Buckling, Angus; Westra, Edze R.

In: FEMS Microbiology Letters, Vol. 366, No. 5, fnz047, 01.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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