CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). In type II CRISPR systems correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (rnc) and this protein. The tracrRNA serves as a guide for ribonuclease 3-aided processing of pre-crRNA. Subsequently Cas9/crRNA/tracrRNA endonucleolytically cleaves linear or circular dsDNA target complementary to the spacer; Cas9 is inactive in the absence of the 2 guide RNAs (gRNA). Cas9 recognizes a short motif in the CRISPR repeat sequences (the PAM or protospacer adjacent motif) to help distinguish self versus nonself, as targets within the bacterial CRISPR locus do not have PAMs. PAM recognition is also required for catalytic activity. Cuts target DNA when Cas9 and gRNAs are mixed (PubMed:24270795, PubMed:26875867). Plays a role in repression of expression of endogenous bacterial lipoprotein FTN_1103. Cas9 plays a possibly non-enzymatic role in the degradation of FTN_1103 mRNA, which is dependent on formation of an RNA:RNA complex of tracrRNA and scaRNA (the latter is not found in all type II CRISPR-Cas systems). Monomer. Binds crRNA and tracrRNA. In culture expression is maximal at 3 hours during mid-log phase. During infection of mouse bone marrow-derived macrophages (BMDM) expression is maximal after 1 hour, when the bacteria is expected to be in the phagosome. The arginine-rich motif (ARM, residues 55-73) plays a role in regulation of at least 1 endogenous gene (FTN_1103). Has a recognition domain (REC, residues 83-858) and a nuclease domain (NUC, residues 1-51 and 859-1629). The crRNA-target DNA twist through the domains in a different manner than in the S.pyogenes and S.aureus orthologs (PubMed:26875867). The NUC lobe has 2 endonuclease domains. The discontinuous RuvC-like domain in NUC cleaves the target DNA noncomplementary to crRNA while the HNH nuclease domain cleaves the target DNA complementary to crRNA (Probable). 100-fold increase in expression of bacterial lipoprotein FTN_1103, increased stimulation of interleukin-6 (Il6) production in a Tlr2-dependent fashion by C57BL/6 mouse bone marrow-derived macrophages. In mice nearly 10(4)-fold less virulent than wild-type bacteria. A double cas9-FTN_1103 disruption significantly decreases Il6 production. Mice immunized with this gene deleted were protected against subsequent infection with wild-type bacteria. The simplicity of the Cas9-gRNAs RNA-directed DNA endonuclease activity may be used to target and modify a DNA sequence of interest (PubMed:24270795). Pre-assembled Cas9, crRNA and tracRNA induces indel formation in targeted genes upon microinjection into mouse zygotes; mutations E1369R/E1449H/R1556A alter PAM recognition and thus enlarge the scope of this protein for genetic engineering, see PDB 5B2Q for the X-ray structure of this variant. The strain deleted for this gene might make a good vaccine candiate (PubMed:26875867). Part of a type II CRISPR-Cas system. Belongs to the CRISPR-associated protein Cas9 family. Subtype II-B subfamily.