0 – -1.5† – - I 1631 TetR Family -1.9 -2.1 – - – - I 1700 Predicted Transcriptional Regulator 2.0 2.9 – - – - II 0051 LuxR Family DNA Binding GDC-941 Domain -1.9 -2.8 – - – - II 0800 AraC Family 1.7 2.2† – - – - II 0854 CRP Family Transcriptional Regulator – 1.6† – -1.5 -1.7 – II 0985 LacI Family -2.5 -2.7† – -2.4 – - II 1022 IclR Family -1.5† -1.8 – -1.9 -2.1 – II 1098 AraC Family -1.8 -2.8 – 1.9 1.5 – I 0446 MarR Family 1.9†
2.9 2.9† – - – I 0518 Cold Shock Protein, CspA 1.6 – -2.0† 1.7 – - I 0720 Sugar Fermentation Stimulation Protein – -2.0 1.7† -1.7† – 1.5† I 0899 Phage-Related DNA Binding Protein Mizoribine order -1.8 -1.5† -1.9† 1.6 – -2.4† I 1098 AsnC Family -1.7 -2.0 -1.6† -1.6 – - I 1291 AraC Family – -1.9 -1.7† 1.7 – - I 1641 TetR Family – - -2.7† -1.7 -1.8 – I 1885 LysR Family – -1.8† -2.3† -1.6 – - II 0127 IclR Family – 1.6† – -1.8 – 1.6† II 0219 IclR Family -3.2 -5.8 -3.8† -1.5† – - II 0657 Transcription Elongation Factor 2.4† 3.1 – - – 2.4† II 0810 ArsR Family – 2.0 – 1.8 1.6† -2.3† A (-) indicates genes excluded for technical reasons or had a fold change of less than 1.5; † genes that did not pass the statistical significance test but showed an average alteration of at least 1.5-fold. 4SC-202 clinical trial Fold change values are the averaged log2 ratio of normalized signal values from two independent statistical analyses. Abbreviations as follows: STM, Signature Tagged Mutagenesis.
The differentially expressed genes were categorized
by clusters of orthologous genes (COGs), obtained from the DOE Joint Genome Institute Integrated Microbial Genomics project http://img.jgi.doe.gov/cgi-bin/pub/main.cgi. This classification revealed categories that were equally altered by both the vjbR mutant and addition of C12-HSL to wildtype bacteria (Fig. 3). For example; defense mechanisms, intracellular trafficking and secretion were highly over-represented when compared to genomic content. Of particular note, genes involved in cell division were found to be over-represented in wildtype bacteria grown in the presence of C12-HSL but not by deletion of vjbR, indicating that C12-HSL Montelukast Sodium regulates cellular division and may play a key role in the intracellular replication of the bacteria. Figure 3 COG functional categories found to be over and under represented by the deletion of vjbR and the addition of C 12 -HSL to wildtype cells, indicated by microarray analyses. Ratios were calculated by comparing the proportion of genes found to be altered by the putative QS component to the total number of genes classified in each COG category present in the B. melitensis genome. Genes found to be altered by deletion of vjbR and treatment with C12-HSL in both wildtype and ΔvjbR backgrounds were compared to data compiled from random mutagenesis screenings, resulting in the identification of 61 genes (Tables 2, 3, 4 and Additional File 3, Table S3) [22, 28, 39].