Background We investigated the single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus and examined its association with microbial, biological and periodontal disease clinical parameters. Methods We annotated a 200Kb-spanning region of 1q12 previously highlighted in a genome-wide association scan among 4,910 European American individuals (SNP rs1633266). Two haplotype blocks were selected. We examined the association of these polymorphisms with data on microbial plaque composition, gingival crevicular fluid (GCF)-interleukin (IL)-1β levels and clinical parameters of periodontal disease. Descriptive analysis of IFI16 and AIM2 protein expression in gingival tissues from healthy (n=2) and chronic periodontitis individuals (n=2) was done via immunohistochemistry. Results The highlighted locus is a 100Kb region containing the interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes. Two haplotype blocks rs6940 and rs1057028 were significantly associated with increased extent bleeding on probing and levels of microorganisms Porphyromonas gingivalis, Tannerella forsythia and Campylobacter rectus (p≤0.05). Haplotype block rs1057028 was also significantly associated with pathogens Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans, increased GCF-IL-1β levels and extent of probing depth≥4mm (p≤0.05). Prevalence of severe periodontitis (biofilm-gingival interface-P3 classification) was positively associated with haplotype block rs1057028. Similar trends were observed for haplotype block rs1057028. IFI16 and AIM2 protein expression was observed in multiple cell types of gingival tissues, including inflammatory cells. Conclusion This study found IFI16 and AIM2 SNPs associated with higher levels periodontal microorganisms and increased percentage of periodontal disease clinical parameters, suggesting the need for functional studies and additional fine-mapping of variants in the 1q12-locus.

The rapid increasing number of completed bacterial genomes provides a good opportunity to compare their proteomes. This study was undertaken to specifically compare and contrast their secretomes—the fraction of the proteome with predicted N-terminal signal sequences, both type I and type II. A total of 176 theoretical bacterial proteomes were examined using the ExProt program. Compared with the Gram-positives, the Gram-negative bacteria were found, on average, to contain a larger number of potential Sec-dependent sequences. In the Gram-negative bacteria but not in the others, there was a positive correlation between proteome size and secretome size, while there was no correlation between secretome size and pathogenicity. Within the Gram-negative bacteria, intracellular pathogens were found to have the smallest secretomes. However, the secretomes of certain bacteria did not fit into the observed pattern. Specifically, the secretome of Borrelia burgdoferi has an unusually large number of putative lipoproteins, and the signal peptides of mycoplasmas show closer sequence similarity to those of the Gram-negative bacteria. Our analysis also suggests that even for a theoretical minimal genome of 300 open reading frames, a fraction of this gene pool (up to a maximum of 20%) may code for proteins with Sec-dependent signal sequences.

Just as in the Eukarya and the Bacteria, members of the Archaea need to export proteins beyond the cell membrane. This would be required to fulfill a variety of essential functions such as nutrient acquisition and biotransformations, maintenance of extracellular structures and more. Apart from the Eukarya and the Bacteria however, members of the Archaea share a number of unique characteristics. Does this uniqueness extend to the protein secretion system? It was the objective of this study to answer this question. To overcome the limited experimental information on secreted proteins in Archaea, this study was carried out by subjecting the available archaeal genomes, which represent halophiles, thermophiles, and extreme thermophiles, to bioinformatics analysis. Specifically, to examine the properties of the secretomes of the Archaea using the ExProt program. A total of 24 genomes were analyzed. Secretomes were found to fall in the range of 6% of total ORFs (Methanopyrus kandleri) to 19% (Halobacterium sp. NRC-1). Methanosarcina acetivorans has the highest fraction of lipoproteins (at 89) and the lowest (at 1) were members of the Thermoplasma, Pyrobaculum aerophilum, and Nanoarchaeum equitans. Based on the Tat consensus sequence, contribution of these secreted proteins to the secretomes were negligible, making up 8 proteins out of a total of 7105 predicted exported proteins. Amino acid composition, an attribute of signal peptides not used as a selection criteria by ExProt, of predicted archaeal signal peptides show that in the haloarchaea secretomes, the frequency of the amino acid Lys is much lower than that seen in bacterial signal peptides, but is compensated for by a higher frequency of Arg. It also showed that higher frequencies for Thr, Val, and Gly contribute to the hydrophobic character in haloarchaeal signal peptides, unlike bacterial signal peptides in which the hydrophobic character is dominated by Leu and Ile.