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Insertion sequences in the CRISPR-Cas system regulate horizontal antimicrobial resistance gene transfer in Shigella

Shuaiyin Chen1, Huiying Liu1, Wenjuan Liang2

  • 1Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

International Journal of Antimicrobial Agents
|October 6, 2018
PubMed

Insights

Multidrug-resistant Shigella strains can inactivate their CRISPR-Cas immune systems using insertion sequences. This allows them to acquire new genes, including antimicrobial resistance, via horizontal gene transfer (HGT).

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Multidrug-resistant Shigella poses a significant public health threat.
  • Antimicrobial resistance genes spread through horizontal gene transfer (HGT).
  • CRISPR-Cas systems provide bacterial immunity but can hinder beneficial gene acquisition.

Purpose of the Study:

  • To investigate how Shigella regulates CRISPR-Cas activity to acquire necessary genes.
  • To understand the role of insertion sequences in modulating CRISPR-Cas function in Shigella.

Main Methods:

  • Identification of insertion sequences (IS) within CRISPR-associated (cas) genes in Shigella strains.
  • Comparative analysis of CRISPR-Cas array spacer numbers in strains with and without IS elements.
  • Construction of an antimicrobial-resistant Shigella strain via electrotransformation to observe CRISPR-Cas system changes.
  • Bioinformatics analysis of IS insertion sites, protein structure, and gene expression.

Main Results:

  • Insertion sequences (IS600, ISSfl2, IS629) were found in cas genes of Shigella.
  • Strains with IS elements and multidrug-resistant isolates exhibited fewer CRISPR-Cas spacers.
  • An insertion sequence (IS600) was identified in the cse2 gene of a constructed antimicrobial-resistant strain.
  • IS600 insertion in cse2 altered protein structure and significantly decreased gene expression.

Conclusions:

  • Insertion sequences play a role in modulating CRISPR-Cas activity in Shigella.
  • CRISPR-Cas system inactivation by IS elements facilitates the acquisition of antimicrobial resistance genes through HGT.
  • This mechanism provides insight into the spread of antibiotic resistance in Shigella.
Keywords:
Antimicrobial resistanceCRISPR-CasHorizontal gene transferIS600Insertion sequenceShigella

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