E transporter FeuABC-YusV. To achieve intracellular iron release, Fe-BB is then hydrolyzed by the Fe-BB esterase BesA and iron is used by the cell [27]. The process of iron transport is controlled by 3 regulatory proteins: Fur, Mta, and Btr. When iron concentration is low, derepression of Fur leads to increased activity of Mta and Btr, which accelerates BB outflow and Fe-BB uptake. In this manner, all the genes related to iron transport are upregulatedupon fusaricidin treatment of B. 
subtilis, robustly stimulating iron transport. We next compared our data with the results from other studies. Cluster analysis was used to determine whether other antibiotic treatments had a similar profile to that of fusaricidin. NO [28], vancomycin (Van) [18], bacitracin (Baci) [29], iron starvation [30], Fe limitation [31], and daptomycin (Dap) [32] were all used in the comparison. As shown in Figure 8, the data from the Fe limitation treatment had the highest similarity to those from our experiment. This 166518-60-1 chemical information suggests that iron is an essential component for bacteria to resist treatment with toxins. Forty additional antibiotics were also chosen to compare with the fusaricidin treatment in this study. This comparison revealed that the treatment of B. subtilis with fusaricidin elicited a profile most similar with that of triclosan (Fig. 9).Mechanisms of Fusaricidins to Bacillus subtilisFigure 9. The clustering analysis between the antibiotic microarray data. Different antibiotics are listed on the top of the figure. The similarities of the genes between the different experiments are indicated in different colors. Low expression is indicated in green; and high expression, in red. doi:10.1371/journal.pone.0050003.gFusaricidin addition could lead B. subtilis’s membrane to be destroyed and more OH produced which affected the biosynthesis of protein and nucleic acid in the cells at the initial phase. However, B. subtilis could recover its growth in the late phase because of the congeries of the cells in the culture (data not shown here). It is suggested that the novel antibactin should stimulate the cells to secrete more and more OH to disturb the growth and prevent the cells to congest simultaneously. The transcriptome analyses indicate that fusaricidin induced sets of genes shown previously to be induced by 50-14-6 exposure to membrane-active compounds. The TCS was significantly induced by fusaricidin, and genetic studies indicated that SigA was sensitive to this change. These results were consistent with the notion that this type of antibiotic acts primarily on the cell membrane [33]. Apparently, B. subtilis is one of microorganisms which is able toalter 24786787 its gene expression pattern in response to fusaricidin to develop resistance to 
antibiotic treatment and some other environmental changing.Supporting InformationTable S1 Gene Differentially expressed genes at 20 and170 min. (XLSX)Author ContributionsConceived and designed the experiments: B-CY. Performed the experiments: YZ W-BY C-YY. Analyzed the data: YZ C-YY. Contributed reagents/materials/analysis tools: W-BY. Wrote the paper: B-CY YZ.
The cAMP binding domain (CBD) is an ancient regulatory module found throughout multiple proteins with diverse functions [1?]. For example, in prokaryotes, a CBD is present in the transcription factor, catabolite activator protein (CAP) [4,5]. In eukaryotes, CBDs are found in Protein Kinase A and G [1,2,6?18], in transport proteins, hyperpolarization activated and cyclicnucleotide modula.E transporter FeuABC-YusV. To achieve intracellular iron release, Fe-BB is then hydrolyzed by the Fe-BB esterase BesA and iron is used by the cell [27]. The process of iron transport is controlled by 3 regulatory proteins: Fur, Mta, and Btr. When iron concentration is low, derepression of Fur leads to increased activity of Mta and Btr, which accelerates BB outflow and Fe-BB uptake. In this manner, all the genes related to iron transport are upregulatedupon fusaricidin treatment of B. subtilis, robustly stimulating iron transport. We next compared our data with the results from other studies. Cluster analysis was used to determine whether other antibiotic treatments had a similar profile to that of fusaricidin. NO [28], vancomycin (Van) [18], bacitracin (Baci) [29], iron starvation [30], Fe limitation [31], and daptomycin (Dap) [32] were all used in the comparison. As shown in Figure 8, the data from the Fe limitation treatment had the highest similarity to those from our experiment. This suggests that iron is an essential component for bacteria to resist treatment with toxins. Forty additional antibiotics were also chosen to compare with the fusaricidin treatment in this study. This comparison revealed that the treatment of B. subtilis with fusaricidin elicited a profile most similar with that of triclosan (Fig. 9).Mechanisms of Fusaricidins to Bacillus subtilisFigure 9. The clustering analysis between the antibiotic microarray data. Different antibiotics are listed on the top of the figure. The similarities of the genes between the different experiments are indicated in different colors. Low expression is indicated in green; and high expression, in red. doi:10.1371/journal.pone.0050003.gFusaricidin addition could lead B. subtilis’s membrane to be destroyed and more OH produced which affected the biosynthesis of protein and nucleic acid in the cells at the initial phase. However, B. subtilis could recover its growth in the late phase because of the congeries of the cells in the culture (data not shown here). It is suggested that the novel antibactin should stimulate the cells to secrete more and more OH to disturb the growth and prevent the cells to congest simultaneously. The transcriptome analyses indicate that fusaricidin induced sets of genes shown previously to be induced by exposure to membrane-active compounds. The TCS was significantly induced by fusaricidin, and genetic studies indicated that SigA was sensitive to this change. These results were consistent with the notion that this type of antibiotic acts primarily on the cell membrane [33]. Apparently, B. subtilis is one of microorganisms which is able toalter 24786787 its gene expression pattern in response to fusaricidin to develop resistance to antibiotic treatment and some other environmental changing.Supporting InformationTable S1 Gene Differentially expressed genes at 20 and170 min. (XLSX)Author ContributionsConceived and designed the experiments: B-CY. Performed the experiments: YZ W-BY C-YY. Analyzed the data: YZ C-YY. Contributed reagents/materials/analysis tools: W-BY. Wrote the paper: B-CY YZ.
The cAMP binding domain (CBD) is an ancient regulatory module found throughout multiple proteins with diverse functions [1?]. For example, in prokaryotes, a CBD is present in the transcription factor, catabolite activator protein (CAP) [4,5]. In eukaryotes, CBDs are found in Protein Kinase A and G [1,2,6?18], in transport proteins, hyperpolarization activated and cyclicnucleotide modula.
