Two spacers from different strains targeted the gene encoding
N-acetylmuramoyl-L-alanine amidase: a CHAP-family NCT-501 clinical trial domain protein found to have lytic ability [49]. Several strains possess spacers matching the gene encoding the glycoside hydrolase (GH) family 25 protein and the non-coding regions in its close vicinity. The GH 25 family comprises lysozyme able to hydrolyse peptidoglycan and two Abi proteins conferring resistance to a broad range of related bacteriocins [15, 50]. It has been suggested that these findings are in agreement with the data showing that G. vaginalis strains produce substances antagonistic to bacterial isolates common to the vaginal microbiome [15, 51]. A substantial part of the spacers targeted non-coding regions or ORF’s encoding hypothetical proteins with undefined functions. Our data suggest that the CRISPR/Cas system was in touch with G. vaginalis HDAC inhibitor DNA that was most probably of chromosomal origin and accessed by the transformation, transduction, or conjugation routes. DNA acquisition and exchange by natural transformation among G. vaginalis strains was detected as a favourable route [22]. Moreover, G. vaginalis strains were found to encode
the competence promoting proteins ComEA, ComEC, and CinA [15]; http://blast.ncbi.nlm.nih.gov/Blast.cgi. Our data on the origin of the spacers detected in the G. vaginalis CRISPR arrays propose the hypothesis that the transfer of genetic material among G. vaginalis Rucaparib strains could be regulated by the CRISPR/Cas mechanism. Circumstances favourable for DNA transfer and CRISPR activity would mean the simultaneous presence of more than one G. vaginalis strain during infection, which is consistent with previous reports [21, 22, 52]. The impact of CRISPR/Cas on the virulence of G. vaginalis could involve the spacer targeting the GH family 25 gene that encodes a product promoting competitive exclusion by the 409–05 strain http://blast.ncbi.nlm.nih.gov/Blast.cgi. The distribution of CRISPR/Cas loci among pathogenic bacteria that incorporate new genetic material, along with virulence genes, through
natural transformation is variable [27, 43]. The incidence of the CRISPR/Cas system among G. vaginalis strains may be determined by the habitat of the bacteria. The low prevalence of viruses in the human endometrium [53] does not promote the acquisition of CRISPR/Cas by G. vaginalis as an adaptive immunity system against foreign DNA. However, the human vagina is a more favourable environment for virus progression, and extravaginal reservoirs have an impact on the distribution of viruses in the vaginal tract [54]. Stem Cells inhibitor Recent papers have demonstrated that pathogenic bacteria may lose CRISPR/Cas under certain selective pressure [55, 56]. The presence of multiple antibiotic resistances is correlated with the loss of CRISPR loci in enterococci [55].