CRISPR‐Cas systems in oral microbiome: From immune defense to physiological regulation

Abstract

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.

Manganese Depletion Leads to Multisystem Changes in the Transcriptome of the Opportunistic Pathogen Streptococcus sanguinis

“…Many of these genes were differentially expressed ( Supplementary Figure S6), which may be due to the intertwined nature of amino acid and carbohydrate metabolism (Radin et al, 2016). We also observed decreased expression of large, contiguous loci encoding ethanolamine utilization (Fox et al, 2009;Kaval and Garsin, 2018;Kaval et al, 2019), a type IV pilus system (Chen et al, 2019), and CRISPR-associated proteins (Makarova et al, 2015;Gong et al, 2020; Supplementary Figure S7), which are all also tied to CcpA-regulation (Bai et al, 2019).…”

Virulence of the Pathogen Porphyromonas gingivalis Is Controlled by the CRISPR-Cas Protein Cas3

“…However, Lum et al showed that although transcription of oral CRISPR loci is relatively ubiquitous, highly expressed CRISPR spacers do not necessarily target the most abundant oral phages ( 42 ). Moreover, recently, new functions, other than defense, have been attributed to CRISPR systems of the oral microbiome ( 43 ). Even though bacteriophages have been isolated from oral bacteria, a bacteriophage for P. gingivalis has yet to be isolated despite the efforts in this area ( 44 , 45 ).…”

Manganese depletion leads to multisystem changes in the transcriptome of the opportunistic pathogenStreptococcus sanguinis

“…CRISPRassociated proteins that make up the CRISPR-Cas system are found in 40% of bacterial species (Makarova et al, 2015). In addition to providing cells with adaptive immunity against foreign mobile elements, including phages and plasmids, these systems have been implicated in modulating oral biofilm development, DNA repair, and DNA uptake (Gong et al, 2020). Of particular interest, the type I and type II CRISPR systems of S. mutans have also been implicated in modulating stress response phenotypes, such as to pH, temperature, and oxidative stress (Serbanescu et al, 2015).…”

“…The type I mutant was able to grow faster in an acidic environment but was more sensitive to H 2 O 2 , paraquat, and SDS (Serbanescu et al, 2015). Oral bacteria tend to have either type I or type II systems (Gong et al, 2020) but S. sanguinis SK36 has a type III system as determined by CRISPRCasFinder (Couvin et al, 2018).…”