The clustered regularly interspaced short palindromic repeats with CRISPR-associated proteins (CRISPR-Cas) system, found in bacteria and archaea, provides sequence-based adaptive immunity against mobile genetic elements, including phages and plasmids. The oral cavity contains approximately 700 prokaryote species harboring known CRISPR-Cas systems, including type I, type II, type III, type V, and type VI, and unidentified CRISPR-Cas systems. There is increasing evidence to suggest that different CRISPR-Cas systems in the human oral microbiome can affect bacterial physiology through different mechanisms. Here, we review the canonical and novel functions of the CRISPR-Cas system, including defense against the invasion of foreign mobile elements, biofilm formation, acquisition of resistance genes, DNA repair, regulation of interspecific competition and intraspecific diversification, stress responses, and gene expression regulation. Overall, the mechanisms involved in CRISPR-Cas systems and their effects on bacterial physiology provide new insights into our understanding of the function and application of methods (including gene editing, modulation of CRISPR-Cas by anti-CRISPR, antimicrobials) on the oral microbiome.© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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