Antibiotic-induced regulon and pathway activation pattern analysis of B. subtilis. The percentages of transcriptionally induced or repressed genes per biosynthetic pathway or regulon are represented in color codes (see color legend at the bottom of the figure). A deregulation of at least 20% of the genes of a pathway-regulon is required for a compound or underexpression effect to be indicated in the figure. Compound and mutant abbreviations can be found in Tables 2 and 3. The pathway and regulon assignments of the genes can be found online at http://www.genedata.com/publications/supplements/. For clarity, the most striking pathway activation patterns have been framed (black). (A) The compound-triggered mRNA profiles all represent long-time exposure experiments (t, 40-min treatments). The compounds and mutants are sorted according to their MOA categories as known from the literature and as concluded from our transcriptome studies (abbreviations for MOA classes are in Table 5). (B) Time-dependent antibiotic-induced regulon and pathway activation pattern analysis of B. subtilis. The numbers after the compound abbreviations symbolize compound treatment times (1 = 10 min; 2 = 40 min). The compounds and mutants are sorted according to their target area assignment (see text). # indicates that, while a significant proportion of the aromatic biosynthesis genes are repressed under condition PTU1 (10-min treatment with the PheST inhibitor), the phenylalanine biosynthesis operon pheAB is slightly induced, which is not the case in any other measured stress condition.

Transcriptional activation pattern of the B. subtilis fatty acid and phospholipid biosynthesis pathway for antibiotic treatment and the modified gene expression due to target underexpression. (A) Mutant with downregulated fabF; (B) treatment of B. subtilis 168 with cerulenin for 10 min; (C) mutant with downregulated accDA; (D) treatment of B. subtilis 168 with MOIB for 10 min (Phylosopher; Genedata). FabF repression and cerulenin treatment mainly induce genes encoding enzymes downstream of the metabolite malonyl-CoA. In contrast to this finding, treatment with MOIB and accDA repression mainly repress those genes. This pathway analysis indicated that cerulenin targets FabF, while MOIB possibly inhibits the ACC. Upregulated genes are colored in red, while downregulated genes are represented by green boxes; see color scale at left. Nonresponsive genes are colored in gray (metabolite names: R, acetyl, isovaleryl, 2-methylbuturyl, or isobutyryl).