Porphyromonas gingivalis and its CRISPR-Cas system

Abstract

The clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated proteins (Cas) are immune systems in prokaryotes present in most Bacteria and Archaea. They provide adaptive immunity against foreign elements such as bacteriophages/viruses, plasmids and transposons. During immunization a small sequence of foreign DNA, a so-called spacer is integrated into the CRISPR locus in the host cell. Spacers are then transcribed into small RNA guides that direct cleavage of foreign DNA by Cas nucleases. Immunization through spacer acquisition is transferred vertically to the progeny. It is possible that this genetic immune system of bacteria participates in modulating the microbiome of 'chronic' periodontitis, in which Porphyromonas gingivalis has been identified as a keystone pathogen causing microbial dysbiosis. An in-depth review of our current knowledge on the CRISPR-Cas systems in P. gingivalis is given in this paper with the attempt to understand how this anaerobic bacterium may protect itself in the periodontal pocket where bacteriophages are abundant and even out-number bacteria. ARTICLE HISTORY

Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update

“…The increased production of CRISPR-RNA is also associated with triggering the stress response, chaperone formation, and horizontal gene transfer among oral bacteria [41][42][43]. The CRISPRs RNA even helps P. gingivalis to induce genomic rearrangements and intercellular recombination that helps to acquire the useful DNA sequences for its survival, limit transposition of insertion sequences and acquire resistance to foreign RNA and DNA [44][45][46][47][48]. Watanabe et al (2017) also observed a highly 'expressed transcripts of CRISPR regulatory small non-coding regulatory RNA (sRNA) in the intergenic sequences (IGS) upstream of CRISPR-associated (cas) gene arrays in P. gingivalis that help to limit the genetic exchange within the biofilm and prevent mutation [42,[45][46][47].…”

“…Watanabe et al (2017) also observed a highly ‘expressed transcripts of CRISPR regulatory small non-coding regulatory RNA (sRNA) in the intergenic sequences (IGS) upstream of CRISPR-associated ( cas ) gene arrays in P. gingivalis that help to limit the genetic exchange within the biofilm and prevent mutation [ 42 , 45 – 47 ]. Another highly upregulated hypothetical proteins, known as ‘HMPREF0389_00967, containing a CHASE3 extracellular sensory domain’, has been observed during F. alocis – P. gingivalis co-infection [ 31 , 48 ]. The HMPREF0389_00967 is found to regulate the production of histidine kinase, adenylate cyclases, and other chemotaxis proteins that helps P. gingivalis to evade the process of phagocytosis [ 31 , 45 – 48 ].…”

“…Another highly upregulated hypothetical proteins, known as ‘HMPREF0389_00967, containing a CHASE3 extracellular sensory domain’, has been observed during F. alocis – P. gingivalis co-infection [ 31 , 48 ]. The HMPREF0389_00967 is found to regulate the production of histidine kinase, adenylate cyclases, and other chemotaxis proteins that helps P. gingivalis to evade the process of phagocytosis [ 31 , 45 – 48 ]. F. alocis – P. gingivalis co-infection is also known to regulate other proteins such as ‘histone cluster proteins and PPIA-peptidyl-prolyl isomerase, transferrin receptor protein 1 (involved in iron transport), transmembrane emp24 domain-containing protein 10, dynein (involved in vesicular protein trafficking), surfeit 4, and solute carrier family proteins’ in the host [ 48 ].…”

“…The HMPREF0389_00967 is found to regulate the production of histidine kinase, adenylate cyclases, and other chemotaxis proteins that helps P. gingivalis to evade the process of phagocytosis [ 31 , 45 – 48 ]. F. alocis – P. gingivalis co-infection is also known to regulate other proteins such as ‘histone cluster proteins and PPIA-peptidyl-prolyl isomerase, transferrin receptor protein 1 (involved in iron transport), transmembrane emp24 domain-containing protein 10, dynein (involved in vesicular protein trafficking), surfeit 4, and solute carrier family proteins’ in the host [ 48 ]. The alteration in the production of these proteins indirectly weakens the innate immune response of the host and favors microbial growth within the tissues.…”

Porphyromonas gingivalis, a Long-Range Pathogen: Systemic Impact and Therapeutic Implications

“…P. gingivalis deploys an extensive arsenal of virulence factors such as lipopolysaccharide, proteases, fimbriae and a CRISPR-Cas system [ 8 , 15 , 16 ]; enabling it to modulate the host immune response to promote its survival through cellular colonization and spreading [ 17 , 18 ]. During the initial phase of infection, this bacterium manipulates the immune system through inhibition of cytokines and chemokines secretion [ 19 , 20 ].…”