The remaining five genes with putative roles in IL-10 modulation comprise a putative 5 gene operon (lp_2647 to lp_2651) encoding Pts19ADCBR, an N-acetyl-galactosamine/glucosamine phosphotransferase system (PTS). Strains harboring these genes were associated with induction of lower amounts of IL-10 by PBMCs. Table 2 L. plantarum genes with putative roles in modulating

PBMC cytokine production. Genes(s) Gene numbera Product Percent Trichostatin A of strains with the gene(s)b Gene-dependent contribution to cytokine stimulationc lp_1953 lp_1953 Hypothetical protein 48 IL-10 1.6-fold ↑ pts19ADCBR lp_2647-2651 N-galactosamine PTS, EIIADCB and transcription regulator, GntR family 33 IL-10 1.7-fold ↓ plnEFI lp_0419-0422 Immunity protein PlnI 81-85 IL-10/IL-12 1.7-fold

↓     Bacteriocin-like peptide PlnF           Bacteriocin-like peptide PlnE       plnG lp_0423 ABC transporter 88 IL-10/IL-12 1.8-fold ↓ lamB lp_3582 Accessory gene Alvocidib regulator protein 43 IL-10/IL-12 1.3-fold ↓ prophage P2b 1 & 21 lp_2460 Prophage P2b protein 21 38 IL-10/IL-12 1.5-fold ↑   lp_2480 Prophage P2b protein 1, integrase       a Gene number on the L. plantarum WCFS1 chromosome [23]. b Percentage of L. plantarum strains containing the gene according to CGH [27, 28]. c Gene-trait matching importance measures (in parentheses) and predicted effects of the gene(s) on the variable and average magnitude and direction (higher or lower) of IL-10 and IL-10/IL-12 amounts. Comparisons between L. plantarum strain-specific CGH profiles and IL-10/IL-12 ratios from PBMCs resulted in the identification of four L. plantarum WCFS1 loci which correlated with IL-10/IL-12 values (Table

2). L. plantarum WCFS1 plnEFI and plnG (lp_419-423) and lamB (lp_3582) were most commonly present Selleckchem MG132 in strains stimulating low IL-10/IL-12 ratios. These genes are under the control of the auto-inducing peptide (AIP)-based quorum sensing (QS) two-component regulatory systems (QS-TCSs) found in L. plantarum [39, 40]. The genes plnEFI and plnG encode two bacteriocin peptides, a bacteriocin immunity protein, and an ATP – Binding Cassette (ABC) transporter [23, 41]. The lamB is the first gene in the L. plantarum lamBDCA operon and shows 30% amino acid identity to the S. aureus AgrD-processing protein AgrB required for AIP modification and export [39]. The other L. plantarum genes associated with specific IL-10/IL-12 ratios are lp_2460 and lp_2480 coding for prophage R-Lp3 remnant proteins P2b protein 21 and 1, respectively [23]. These genes are conserved among L. plantarum strains stimulating high IL-10/IL-12 ratios in PBMCs. The functions of prophage R-Lp3 and other complete prophages in L. plantarum WCFS1 genome are not known [42]. Because the different prophages found in L. plantarum WCFS1 share high levels of sequence homology and potential Selleckchem S3I-201 functional redundancy [42], these genes were not examined further. Verification of the roles of the candidate genes in immunomodulation To validate the influence of the candidate L.