Tic pathway has been identified and characterized in Paenibacillus polymyxa PKB1 [12]. It is intriguing that upstream of this cluster is a 531-bp ORF encoding a putative protein of 177 amino acids; this protein exhibits greatest similarity to ymcC. The gene ymcC of B. subtilis also precedes a cluster of putative polyketide synthase genes. Taken together, these findings suggest that the membrane protein YmcC, which is regulated by the sW factor, may play a role in the action of antibiotics on bacteria. The BacLight kit from Molecular Probes, Inc. (Eugene, Oreg.) was also used to examine fusaricidin-dependent membrane damage, as described by Hilliard [13]. In our previous study, cell membrane integrity damage was observed with B. subtilis 168 by fusaricidins at 46 MIC, whereas no damage was observed with the drug-free control. We subsequently confirmedMechanisms of Fusaricidins to Bacillus subtilisTable 1. The MIPS analysis of the differential genes at 20 min.FUNCTIONAL CATEGORY 01.01.03.03 metabolism of proline 01.01.03.03.01 biosynthesis of proline 01.01.09.07 metabolism of histidine 01.01.09.07.01 biosynthesis of histidine 01.03 nucleotide/nucleoside/nucleobase metabolism 01.03.01 purine nucleotide/nucleoside/nucleobase metabolism 01.03.01.03 purine nucleotide/nucleoside/nucleobase anabolism 01.03.04 pyrimidine nucleotide/nucleoside/nucleobase metabolism 02.25 oxidation of fatty acids 20 CELLULAR TRANSPORT, TRANSPORT FACILITIES, AND TRANSPORT ROUTES 20.01 1485-00-3 site transported compounds (substrates) 20.01.01 23388095 ion transport 20.01.01.01 cation transport (H+, Na+, K+, Ca2+, NH4+, etc.) 20.01.01.01.01 heavy metal ion transport (Cu+, Fe3+, etc.) 20.01.07 amino acid/amino acid derivatives transport 20.01.17 nucleotide/nucleoside/nucleobase transport 20.01.27 drug/toxin transport 20.03 transport facilities 20.03.02 carrier (electrochemical potential-driven transport) 20.03.02.02 symporter 20.03.02.02.01 proton driven symporter 20.03.02.02.02 sodium driven symporter 20.09 transport routes 20.09.18 cellular import 32 CELL RESCUE, DEFENSE, AND VIRULENCE 32.01 stress response 32.01.01 oxidative stress response 32.07 detoxification 32.07.05 detoxification by export 32.07.07 oxygen and radical detoxification 32.07.07.01 catalase reaction 34 INTERACTION WITH THE ENVIRONMENT 34.01 homeostasis 34.01.01 homeostasis of cations 70.30 prokaryotic cytoplasmic membrane doi:10.1371/journal.pone.0050003.tP VALUE 7.69E-03 5.21E-03 1.94E-02 1.94E-02 3.01E-03 1.52E-03 1.34E-07 2.98E-02 7.69E-03 9.41E-04 1.19E-05 4.51E-03 1.22E-03 1.62E-02 2.73E-02 2.77E-02 1.97E-02 1.98E-02 7.36E-04 5.60E-04 7.85E-03 1.63E-02 3.51E-04 7.13E-04 6.00E-04 7.49E-06 4.62E-03 8.33E-04 1.55E-02 1.61E-04 1.72E-02 4.61E-02 1.12E-03 3.22E-04 1.40E-using 2 independent assays (BacLight assay and transcriptome profiling) and various antibiotic concentrations (0.6 to 46 MIC) at which the MoA of fusaricidin is likely to involve membrane damage. The function of differentially expressed genes could be divided into 2 categories: one is involved in the function of cell membrane (yceD, ymcC, yuaFG, ythP, and yojB), and the other is mainly related to detoxification, multidrug resistance, and cell protection (yceE, ydjP, and yeaA). yceD is involved in biofilm formation and was overexpressed by 3-fold after fusaricidin treatment, suggesting that accelerated biofilm formation may contribute to the HIV-RT inhibitor 1 resistance to toxins [14]. In Escherichia coli, the 1662274 methionine sulfoxide reductase YeaA has an important function in.Tic pathway has been identified and characterized in Paenibacillus polymyxa PKB1 [12]. It is intriguing that upstream of this cluster is a 531-bp ORF encoding a putative protein of 177 amino acids; this protein exhibits greatest similarity to ymcC. The gene ymcC of B. subtilis also precedes a cluster of putative polyketide synthase genes. Taken together, these findings suggest that the membrane protein YmcC, which is regulated by the sW factor, may play a role in the action of antibiotics on bacteria. The BacLight kit from Molecular Probes, Inc. (Eugene, Oreg.) was also used to examine fusaricidin-dependent membrane damage, as described by Hilliard [13]. In our previous study, cell membrane integrity damage was observed with B. subtilis 168 by fusaricidins at 46 MIC, whereas no damage was observed with the drug-free control. We subsequently confirmedMechanisms of Fusaricidins to Bacillus subtilisTable 1. The MIPS analysis of the differential genes at 20 min.FUNCTIONAL CATEGORY 01.01.03.03 metabolism of proline 01.01.03.03.01 biosynthesis of proline 01.01.09.07 metabolism of histidine 01.01.09.07.01 biosynthesis of histidine 01.03 nucleotide/nucleoside/nucleobase metabolism 01.03.01 purine nucleotide/nucleoside/nucleobase metabolism 01.03.01.03 purine nucleotide/nucleoside/nucleobase anabolism 01.03.04 pyrimidine nucleotide/nucleoside/nucleobase metabolism 02.25 oxidation of fatty acids 20 CELLULAR TRANSPORT, TRANSPORT FACILITIES, AND TRANSPORT ROUTES 20.01 transported compounds (substrates) 20.01.01 23388095 ion transport 20.01.01.01 cation transport (H+, Na+, K+, Ca2+, NH4+, etc.) 20.01.01.01.01 heavy metal ion transport (Cu+, Fe3+, etc.) 20.01.07 amino acid/amino acid derivatives transport 20.01.17 nucleotide/nucleoside/nucleobase transport 20.01.27 drug/toxin transport 20.03 transport facilities 20.03.02 carrier (electrochemical potential-driven transport) 20.03.02.02 symporter 20.03.02.02.01 proton driven symporter 20.03.02.02.02 sodium driven symporter 20.09 transport routes 20.09.18 cellular import 32 CELL RESCUE, DEFENSE, AND VIRULENCE 32.01 stress response 32.01.01 oxidative stress response 32.07 detoxification 32.07.05 detoxification by export 32.07.07 oxygen and radical detoxification 32.07.07.01 catalase reaction 34 INTERACTION WITH THE ENVIRONMENT 34.01 homeostasis 34.01.01 homeostasis of cations 70.30 prokaryotic cytoplasmic membrane doi:10.1371/journal.pone.0050003.tP VALUE 7.69E-03 5.21E-03 1.94E-02 1.94E-02 3.01E-03 1.52E-03 1.34E-07 2.98E-02 7.69E-03 9.41E-04 1.19E-05 4.51E-03 1.22E-03 1.62E-02 2.73E-02 2.77E-02 1.97E-02 1.98E-02 7.36E-04 5.60E-04 7.85E-03 1.63E-02 3.51E-04 7.13E-04 6.00E-04 7.49E-06 4.62E-03 8.33E-04 1.55E-02 1.61E-04 1.72E-02 4.61E-02 1.12E-03 3.22E-04 1.40E-using 2 independent assays (BacLight assay and transcriptome profiling) and various antibiotic concentrations (0.6 to 46 MIC) at which the MoA of fusaricidin is likely to involve membrane damage. The function of differentially expressed genes could be divided into 2 categories: one is involved in the function of cell membrane (yceD, ymcC, yuaFG, ythP, and yojB), and the other is mainly related to detoxification, multidrug resistance, and cell protection (yceE, ydjP, and yeaA). yceD is involved in biofilm formation and was overexpressed by 3-fold after fusaricidin treatment, suggesting that accelerated biofilm formation may contribute to the resistance to toxins [14]. In Escherichia coli, the 1662274 methionine sulfoxide reductase YeaA has an important function in.
