Transcript levels peaked in ML phase and decreased gradually to their lowest levels in S phase. These six clusters differ in their basal

level of expression in L phase. The genes assigned to cluster 5 were expressed at low levels in ML phase, whereas genes in cluster 14 had very high transcripts Selleck JIB04 in ML phase. Cluster 5 contains genes involved in multiple cellular and metabolic processes, whereas cluster 14 genes are involved predominantly in synthesis of ribosomal proteins. Clusters 12–14 contain genes encoding RNA polymerase subunits (gbs0084, gbs0105, gbs0156/7, gbs0302) that are down regulated from -2.3 to -10 times, which likely indicates a slowing of gene transcription. RpoD (gbs1496, encoding the major σ70) is also down regulated (~-3×). The RpoE subunit (gbs0105) plays a role in the development of sepsis during GBS infection [22], and its down regulation during growth might have consequences for GBS virulence. S phase related genes Histone Methyltransferase inhibitor We identified a group of known stress response genes present in clusters 1–4 that were significantly up-regulated in S phase, including hrcA, grpE,

dnaK (gbs0094–96), clpE, and clpL (gbs0535 and gbs1376). Transcription of genes putatively involved in the stress response such as Gls24 and universal stress response family proteins gbs1202/1204, gbs1721, and gbs1778 were also elevated in S phase compared to ML phase (Table 1). Two apparent operons responsible for arginine/ornithine transport and metabolism were also among the group of highly transcribed many S phase genes. One operon (gbs2083–2085) encodes an arginine/ornithine antiporter, carbamate kinase, and ornithine carbamoyltransferase, respectively, and is up-regulated 350 to >1,000 times. The second operon (gbs2122–2126) encodes arginine deiminase, a second ornithine

carbamoyltransferase, a second arginine/ornithine antiporter, and another carbamate kinase and is up-regulated ~55 to 150 times. Enzymes encoded by genes in these apparent operons are involved in arginine fermentation via the arginine deiminase pathway. They allow GBS to use arginine as an energy source after simple carbohydrates are exhausted from the medium, as would occur during stationary phase. On the other hand, activation of arginine deiminase Eltanexor ic50 pathway might have protective function against acidic conditions in a way similar to oral Streptococci [23] as we observed decrease of pH from about 7.9 to 5.5 between ML and S growth phases. Metabolic changes toward the utilization of increasingly complex nutrient and carbon sources (see below) can be reflected by changes in utilization of simple carbohydrates (drop in the glucose concentration in the medium from ~300 mg/ml in ML to non detectable level in S) and by changes in transcription of the glpKDF (gbs0263–5, +45 to +63 times), a putative operon responsible for glycerol uptake and utilization.