scholarly journals A Mutation of the RNA Polymerase β′ Subunit (rpoC) Confers Cephalosporin Resistance in Bacillus subtilis

2012 ◽  
Vol 57 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Yong Heon Lee ◽  
Ki Hyun Nam ◽  
John D. Helmann
Keyword(s):  
Bacillus Subtilis ◽  
Rna Polymerase ◽  
Cell Envelope ◽  
Control Cell ◽  
Triple Mutant ◽  
Content Type ◽  
Σ Factor ◽  
Elevated Expression ◽  
Regulatory Effects ◽  
High Level

ABSTRACTIn bacteria, mutations affecting the major catalytic subunits of RNA polymerase (encoded byrpoBandrpoC) emerge in response to a variety of selective pressures. Here we isolated aBacillus subtilisstrain with high-level resistance to cefuroxime (CEF). Whole-genome resequencing revealed only one missense mutation affecting an invariant residue in close proximity to the C-terminal DNA-binding domain of RpoC (G1122D). Genetic reconstruction experiments demonstrate that this substitution is sufficient to confer CEF resistance. The G1122D mutation leads to elevated expression of stress-responsive regulons, including those of extracytoplasmic function (ECF) σ factors (σM, σW, and σX) and the general stress σ factor (σB). The increased CEF resistance of therpoCG1122Dstrain is lost in thesigM rpoCG1122Ddouble mutant, consistent with a major role for σMin CEF resistance. However, asigMmutant is very sensitive to CEF, and this sensitivity is still reduced by the G1122D mutation, suggesting that other regulatory effects are also important. Indeed, the ability of the G1122D mutation to increase CEF resistance is further reduced in a triple mutant strain lacking three ECF σ factors (σM, σW, and σX), which are known from prior studies to control overlapping sets of genes. Collectively, our findings highlight the ability of mutations in RNA polymerase to confer antibiotic resistance by affecting the activity of alternative σ factors that control cell envelope stress-responsive regulons.

scholarly journals Bacillus subtilis σVConfers Lysozyme Resistance by Activation of Two Cell Wall Modification Pathways, Peptidoglycan O-Acetylation and d-Alanylation of Teichoic Acids

2011 ◽  
Vol 193 (22) ◽  
pp. 6223-6232 ◽  
Author(s):  
Veronica Guariglia-Oropeza ◽  
John D. Helmann
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Double Mutant ◽  
Cell Envelope ◽  
Intrinsic Resistance ◽  
Triple Mutant ◽  
Cell Wall Modification ◽  
Content Type ◽  
Teichoic Acids ◽  
Σ Factor

The seven extracytoplasmic function (ECF) sigma (σ) factors ofBacillus subtilisare broadly implicated in resistance to antibiotics and other cell envelope stressors mediated, in part, by regulation of cell envelope synthesis and modification enzymes. We here define the regulon of σVas including at least 20 operons, many of which are also regulated by σM, σX, or σW. The σVregulon is strongly and specifically induced by lysozyme, and this induction is key to the intrinsic resistance ofB. subtilisto lysozyme. Strains with null mutations in eithersigVor all seven ECF σ factor genes (Δ7ECF) have essentially equal increases in sensitivity to lysozyme. Induction of σVin the Δ7ECF background restores lysozyme resistance, whereas induction of σM, σX, or σWdoes not. Lysozyme resistance results from the ability of σVto activate the transcription of two operons: the autoregulatedsigV-rsiV-oatA-yrhKoperon anddltABCDE. Genetic analyses reveal thatoatAanddltare largely redundant with respect to lysozyme sensitivity: single mutants are not affected in lysozyme sensitivity, whereas anoatA dltAdouble mutant is as sensitive as asigVnull strain. Moreover, thesigV oatA dltAtriple mutant is no more sensitive than theoatA dltAdouble mutant, indicating that there are no other σV-dependent genes necessary for lysozyme resistance. Thus, we suggest that σVconfers lysozyme resistance by the activation of two cell wall modification pathways: O-acetylation of peptidoglycan catalyzed by OatA andd-alanylation of teichoic acids by DltABCDE.

scholarly journals Transcriptomic and Phenotypic Characterization of a Bacillus subtilis Strain without Extracytoplasmic Function σ Factors

2010 ◽  
Vol 192 (21) ◽  
pp. 5736-5745 ◽  
Author(s):  
Yun Luo ◽  
Kei Asai ◽  
Yoshito Sadaie ◽  
John D. Helmann
Keyword(s):  
Bacillus Subtilis ◽  
Cell Envelope ◽  
Dominant Role ◽  
Phenotypic Characterization ◽  
Subtilis Strain ◽  
Intrinsic Resistance ◽  
Triple Mutant ◽  
Phenotypic Differences ◽  
Σ Factor

ABSTRACT Bacillus subtilis encodes seven extracytoplasmic function (ECF) σ factors. Three (σM, σW, and σX) mediate responses to cell envelope-active antibiotics. The functions of σV, σY, σZ, and σYlaC remain largely unknown, and strong inducers of these σ factors and their regulons have yet to be defined. Here, we define transcriptomic and phenotypic differences under nonstress conditions between a strain carrying deletions in all seven ECF σ factor genes (the Δ7ECF mutant), a ΔMWX triple mutant, and the parental 168 strain. Our results identify >80 genes as at least partially dependent on ECF σ factors, and as expected, most of these are dependent on σM, σW, or σX, which are active at a significant basal level during growth. Several genes, including the eps operon encoding enzymes for exopolysaccharide (EPS) production, were decreased in expression in the Δ7ECF mutant but affected less in the ΔMWX mutant. Consistent with this observation, the Δ7ECF mutant (but not the ΔMWX mutant) showed reduced biofilm formation. Extending previous observations, we also note that the ΔMWX mutant is sensitive to a variety of antibiotics and the Δ7ECF mutant is either as sensitive as, or slightly more sensitive than, the ΔMWX strain to these stressors. These findings emphasize the overlapping nature of the seven ECF σ factor regulons in B. subtilis, confirm that three of these (σM, σW, and σX) play the dominant role in conferring intrinsic resistance to antibiotics, and provide initial insights into the roles of the remaining ECF σ factors.

scholarly journals Depletion of Undecaprenyl Pyrophosphate Phosphatases Disrupts Cell Envelope Biogenesis in Bacillus subtilis

2016 ◽  
Vol 198 (21) ◽  
pp. 2925-2935 ◽  
Author(s):  
Heng Zhao ◽  
Yingjie Sun ◽  
Jason M. Peters ◽  
Carol A. Gross ◽  
Ethan C. Garner ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Transcriptional Repression ◽  
Cell Envelope ◽  
Turgor Pressure ◽  
Teichoic Acid ◽  
Lethal Gene ◽  
Genetic Redundancy ◽  
Wall Teichoic Acid ◽  
Content Type ◽  
Lipid Ii

ABSTRACTThe integrity of the bacterial cell envelope is essential to sustain life by countering the high turgor pressure of the cell and providing a barrier against chemical insults. InBacillus subtilis, synthesis of both peptidoglycan and wall teichoic acids requires a common C55lipid carrier, undecaprenyl-pyrophosphate (UPP), to ferry precursors across the cytoplasmic membrane. The synthesis and recycling of UPP requires a phosphatase to generate the monophosphate form Und-P, which is the substrate for peptidoglycan and wall teichoic acid synthases. Using an optimizedclusteredregularlyinterspacedshortpalindromicrepeat (CRISPR) system with catalytically inactive (“dead”)CRISPR-associated protein9(dCas9)-based transcriptional repression system (CRISPR interference [CRISPRi]), we demonstrate thatB. subtilisrequires either of two UPP phosphatases, UppP or BcrC, for viability. We show that a third predicted lipid phosphatase (YodM), with homology to diacylglycerol pyrophosphatases, can also support growth when overexpressed. Depletion of UPP phosphatase activity leads to morphological defects consistent with a failure of cell envelope synthesis and strongly activates the σM-dependent cell envelope stress response, includingbcrC, which encodes one of the two UPP phosphatases. These results highlight the utility of an optimized CRISPRi system for the investigation of synthetic lethal gene pairs, clarify the nature of theB. subtilisUPP-Pase enzymes, and provide further evidence linking the σMregulon to cell envelope homeostasis pathways.IMPORTANCEThe emergence of antibiotic resistance among bacterial pathogens is of critical concern and motivates efforts to develop new therapeutics and increase the utility of those already in use. The lipid II cycle is one of the most frequently targeted processes for antibiotics and has been intensively studied. Despite these efforts, some steps have remained poorly defined, partly due to genetic redundancy. CRISPRi provides a powerful tool to investigate the functions of essential genes and sets of genes. Here, we used an optimized CRISPRi system to demonstrate functional redundancy of two UPP phosphatases that are required for the conversion of the initially synthesized UPP lipid carrier to Und-P, the substrate for the synthesis of the initial lipid-linked precursors in peptidoglycan and wall teichoic acid synthesis.

scholarly journals Noc Corrals Migration of FtsZ Protofilaments during Cytokinesis in Bacillus subtilis

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuanchen Yu ◽  
Jinsheng Zhou ◽  
Frederico J. Gueiros-Filho ◽  
Daniel B. Kearns ◽  
Stephen C. Jacobson
Keyword(s):  
Bacillus Subtilis ◽  
Cell Division ◽  
Fluorescence Microscopy ◽  
Control Cell ◽  
Time Lapse ◽  
Ring Formation ◽  
Microfluidic Channels ◽  
Content Type ◽  
The Future ◽  
Z Ring

ABSTRACT Bacteria that divide by binary fission form FtsZ rings at the geometric midpoint of the cell between the bulk of the replicated nucleoids. In Bacillus subtilis, the DNA- and membrane-binding Noc protein is thought to participate in nucleoid occlusion by preventing FtsZ rings from forming over the chromosome. To explore the role of Noc, we used time-lapse fluorescence microscopy to monitor FtsZ and the nucleoid of cells growing in microfluidic channels. Our data show that Noc does not prevent de novo FtsZ ring formation over the chromosome nor does Noc control cell division site selection. Instead, Noc corrals FtsZ at the cytokinetic ring and reduces migration of protofilaments over the chromosome to the future site of cell division. Moreover, we show that FtsZ protofilaments travel due to a local reduction in ZapA association, and the diffuse FtsZ rings observed in the Noc mutant can be suppressed by ZapA overexpression. Thus, Noc sterically hinders FtsZ migration away from the Z-ring during cytokinesis and retains FtsZ at the postdivisional polar site for full disassembly by the Min system. IMPORTANCE In bacteria, a condensed structure of FtsZ (Z-ring) recruits cell division machinery at the midcell, and Z-ring formation is discouraged over the chromosome by a poorly understood phenomenon called nucleoid occlusion. In B. subtilis, nucleoid occlusion has been reported to be mediated, at least in part, by the DNA-membrane bridging protein, Noc. Using time-lapse fluorescence microscopy of cells growing in microchannels, we show that Noc neither protects the chromosome from proximal Z-ring formation nor determines the future site of cell division. Rather, Noc plays a corralling role by preventing protofilaments from leaving a Z-ring undergoing cytokinesis and traveling over the nucleoid.

scholarly journals σIfromBacillus subtilis: Impact on Gene Expression and Characterization of σI-Dependent Transcription That Requires New Types of Promoters with Extended −35 and −10 Elements

2018 ◽  
Vol 200 (17) ◽  
Author(s):  
Olga Ramaniuk ◽  
Martin Převorovský ◽  
Jiří Pospíšil ◽  
Dragana Vítovská ◽  
Olga Kofroňová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Iron Metabolism ◽  
Transcription Initiation ◽  
Iron Homeostasis ◽  
Model Organism ◽  
Content Type ◽  
Σ Factor

ABSTRACTThe σIsigma factor fromBacillus subtilisis a σ factor associated with RNA polymerase (RNAP) that was previously implicated in adaptation of the cell to elevated temperature. Here, we provide a comprehensive characterization of this transcriptional regulator. By transcriptome sequencing (RNA-seq) of wild-type (wt) and σI-null strains at 37°C and 52°C, we identified ∼130 genes affected by the absence of σI. Further analysis revealed that the majority of these genes were affected indirectly by σI. The σIregulon, i.e., the genes directly regulated by σI, consists of 16 genes, of which eight (thedhbandykuoperons) are involved in iron metabolism. The involvement of σIin iron metabolism was confirmed phenotypically. Next, we set up anin vitrotranscription system and defined and experimentally validated the promoter sequence logo that, in addition to −35 and −10 regions, also contains extended −35 and −10 motifs. Thus, σI-dependent promoters are relatively information rich in comparison with most other promoters. In summary, this study supplies information about the least-explored σ factor from the industrially important model organismB. subtilis.IMPORTANCEIn bacteria, σ factors are essential for transcription initiation. Knowledge about their regulons (i.e., genes transcribed from promoters dependent on these σ factors) is the key for understanding how bacteria cope with the changing environment and could be instrumental for biotechnologically motivated rewiring of gene expression. Here, we characterize the σIregulon from the industrially important model Gram-positive bacteriumBacillus subtilis. We reveal that σIaffects expression of ∼130 genes, of which 16 are directly regulated by σI, including genes encoding proteins involved in iron homeostasis. Detailed analysis of promoter elements then identifies unique sequences important for σI-dependent transcription. This study thus provides a comprehensive view on this underexplored component of theB. subtilistranscription machinery.

scholarly journals Environment Shapes the Accessible Daptomycin Resistance Mechanisms in Enterococcus faecium

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Amy G. Prater ◽  
Heer H. Mehta ◽  
Abigael J. Kosgei ◽  
William R. Miller ◽  
Truc T. Tran ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Cell Envelope ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Clinical Strain ◽  
Content Type ◽  
Component Cell ◽  
Evolutionary Trajectories ◽  
High Level ◽  
Cell Envelopes

ABSTRACT Daptomycin binds to bacterial cell membranes and disrupts essential cell envelope processes, leading to cell death. Bacteria respond to daptomycin by altering their cell envelopes to either decrease antibiotic binding to the membrane or by diverting binding away from septal targets. In Enterococcus faecalis, daptomycin resistance is typically coordinated by the three-component cell envelope stress response system, LiaFSR. Here, studying a clinical strain of multidrug-resistant Enterococcus faecium containing alleles associated with activation of the LiaFSR signaling pathway, we found that specific environments selected for different evolutionary trajectories, leading to high-level daptomycin resistance. Planktonic environments favored pathways that increased cell surface charge via yvcRS upregulation of dltABCD and mprF, causing a reduction in daptomycin binding. Alternatively, environments favoring complex structured communities, including biofilms, evolved both diversion and repulsion strategies via divIVA and oatA mutations, respectively. Both environments subsequently converged on cardiolipin synthase (cls) mutations, suggesting the importance of membrane modification across strategies. Our findings indicate that E. faecium can evolve diverse evolutionary trajectories to daptomycin resistance that are shaped by the environment to produce a combination of resistance strategies. The accessibility of multiple and different biochemical pathways simultaneously suggests that the outcome of daptomycin exposure results in a polymorphic population of resistant phenotypes, making E. faecium a recalcitrant nosocomial pathogen.

scholarly journals Modular Organization of the NusA- and NusG-Stimulated RNA Polymerase Pause Signal That Participates in the Bacillus subtilis trp Operon Attenuation Mechanism

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
Smarajit Mondal ◽  
Alexander V. Yakhnin ◽  
Paul Babitzke
Keyword(s):  
Bacillus Subtilis ◽  
Rna Polymerase ◽  
Untranslated Region ◽  
Modular Organization ◽  
Additional Time ◽  
Nascent Transcript ◽  
Content Type ◽  
Attenuation Mechanism ◽  
Transcription Attenuation ◽  
Rna Hairpin

ABSTRACT The Bacillus subtilis trpEDCFBA operon is regulated by a transcription attenuation mechanism in which tryptophan-activated TRAP binds to the nascent transcript and blocks the formation of an antiterminator structure such that the formation of an overlapping intrinsic terminator causes termination in the 5′ untranslated region (5′ UTR). In the absence of bound TRAP, the antiterminator forms and transcription continues into the trp genes. RNA polymerase pauses at positions U107 and U144 in the 5′ UTR. The general transcription elongation factors NusA and NusG stimulate pausing at both positions. NusG-stimulated pausing at U144 requires sequence-specific contacts with a T tract in the nontemplate DNA (ntDNA) strand within the paused transcription bubble. Pausing at U144 participates in a trpE translation repression mechanism. Since U107 just precedes the critical overlap between the antiterminator and terminator structures, pausing at this position is thought to participate in attenuation. Here we carried out in vitro pausing and termination experiments to identify components of the U107 pause signal and to determine whether pausing affects the termination efficiency in the 5′ UTR. We determined that the U107 and U144 pause signals are organized in a modular fashion containing distinct RNA hairpin, U-tract, and T-tract components. NusA-stimulated pausing was affected by hairpin strength and the U-tract sequence, whereas NusG-stimulated pausing was affected by hairpin strength and the T-tract sequence. We also determined that pausing at U107 results in increased TRAP-dependent termination in the 5′ UTR, implying that NusA- and NusG-stimulated pausing participates in the trp operon attenuation mechanism by providing additional time for TRAP binding. IMPORTANCE The expression of several bacterial operons is controlled by regulated termination in the 5′ untranslated region (5′ UTR). Transcription attenuation is defined as situations in which the binding of a regulatory molecule promotes transcription termination in the 5′ UTR, with the default being transcription readthrough into the downstream genes. RNA polymerase pausing is thought to participate in several attenuation mechanisms by synchronizing the position of RNA polymerase with RNA folding and/or regulatory factor binding, although this has only been shown in a few instances. We found that NusA- and NusG-stimulated pausing participates in the attenuation mechanism controlling the expression of the Bacillus subtilis trp operon by increasing the TRAP-dependent termination efficiency. The pause signal is organized in a modular fashion containing RNA hairpin, U-tract, and T-tract components.

scholarly journals Exploring the Amino Acid Residue Requirements of the RNA Polymerase (RNAP) α Subunit C-Terminal Domain for Productive Interaction between Spx and RNAP of Bacillus subtilis

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
Cierra A. Birch ◽  
Madison J. Davis ◽  
Lea Mbengi ◽  
Peter Zuber
Keyword(s):  
Escherichia Coli ◽  
Bacillus Subtilis ◽  
Amino Acid ◽  
Dna Binding ◽  
Rna Polymerase ◽  
Α Subunit ◽  
Stress Induction ◽  
Content Type ◽  
Terminal Domain ◽  
Codon Substitution

ABSTRACT Bacillus subtilis Spx is a global transcriptional regulator that is conserved among Gram-positive bacteria, in which Spx is required for preventing oxidatively induced proteotoxicity. Upon stress induction, Spx engages RNA polymerase (RNAP) through interaction with the C-terminal domain of the rpoA-encoded RNAP α subunit (αCTD). Previous mutational analysis of rpoA revealed that substitutions of Y263 in αCTD severely impaired Spx-activated transcription. Attempts to substitute alanine for αCTD R261, R268, R289, E255, E298, and K294 were unsuccessful, suggesting that these residues are essential. To determine whether these RpoA residues were required for productive Spx-RNAP interaction, we ectopically expressed the putatively lethal rpoA mutant alleles in the rpoAY263C mutant, where “Y263C” indicates the amino acid change that results from mutation of the allele. By complementation analysis, we show that Spx-bound αCTD amino acid residues are not essential for Spx-activated transcription in vivo but that R261A, E298A, and E255A mutants confer a partial defect in NaCl-stress induction of Spx-controlled genes. In addition, strains expressing rpoAE255A are defective in disulfide stress resistance and produce RNAP having a reduced affinity for Spx. The E255 residue corresponds to Escherichia coli αD259, which has been implicated in αCTD-σ70 interaction (σ70 R603, corresponding to R362 of B. subtilis σA). However, the combined rpoAE255A and sigAR362A mutations have an additive negative effect on Spx-dependent expression, suggesting the residues' differing roles in Spx-activated transcription. Our findings suggest that, while αCTD is essential for Spx-activated transcription, Spx is the primary DNA-binding determinant of the Spx-αCTD complex. IMPORTANCE Though extensively studied in Escherichia coli, the role of αCTD in activator-stimulated transcription is largely uncharacterized in Bacillus subtilis. Here, we conduct phenotypic analyses of putatively lethal αCTD alanine codon substitution mutants to determine whether these residues function in specific DNA binding at the Spx-αCTD-DNA interface. Our findings suggest that multisubunit RNAP contact to Spx is optimal for activation while Spx fulfills the most stringent requirement of upstream promoter binding. Furthermore, several αCTD residues targeted for mutagenesis in this study are conserved among many bacterial species and thus insights on their function in other regulatory systems may be suggested herein.

scholarly journals Spore Heat Activation Requirements and Germination Responses Correlate with Sequences of Germinant Receptors and with the Presence of a Specific spoVA2mob Operon in Foodborne Strains of Bacillus subtilis

2017 ◽  
Vol 83 (7) ◽  
Author(s):  
Antonina O. Krawczyk ◽  
Anne de Jong ◽  
Jimmy Omony ◽  
Siger Holsappel ◽  
Marjon H. J. Wells-Bennik ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Heat Resistance ◽  
Spore Germination ◽  
Food Industry ◽  
Heat Treatments ◽  
Phenotypic Traits ◽  
Content Type ◽  
Heat Resistant ◽  
Heat Activation ◽  
High Level

ABSTRACT Spore heat resistance, germination, and outgrowth are problematic bacterial properties compromising food safety and quality. Large interstrain variation in these properties makes prediction and control of spore behavior challenging. High-level heat resistance and slow germination of spores of some natural Bacillus subtilis isolates, encountered in foods, have been attributed to the occurrence of the spoVA 2mob operon carried on the Tn1546 transposon. In this study, we further investigate the correlation between the presence of this operon in high-level-heat-resistant spores and their germination efficiencies before and after exposure to various sublethal heat treatments (heat activation, or HA), which are known to significantly improve spore responses to nutrient germinants. We show that high-level-heat-resistant spores harboring spoVA 2mob required higher HA temperatures for efficient germination than spores lacking spoVA 2mob. The optimal spore HA requirements additionally depended on the nutrients used to trigger germination, l-alanine (l-Ala), or a mixture of l-asparagine, d-glucose, d-fructose, and K+ (AGFK). The distinct HA requirements of these two spore germination pathways are likely related to differences in properties of specific germinant receptors. Moreover, spores that germinated inefficiently in AGFK contained specific changes in sequences of the GerB and GerK germinant receptors, which are involved in this germination response. In contrast, no relation was found between transcription levels of main germination genes and spore germination phenotypes. The findings presented in this study have great implications for practices in the food industry, where heat treatments are commonly used to inactivate pathogenic and spoilage microbes, including bacterial spore formers. IMPORTANCE This study describes a strong variation in spore germination capacities and requirements for a heat activation treatment, i.e., an exposure to sublethal heat that increases spore responsiveness to nutrient germination triggers, among 17 strains of B. subtilis, including 9 isolates from spoiled food products. Spores of industrial foodborne isolates exhibited, on average, less efficient and slower germination responses and required more severe heat activation than spores from other sources. High heat activation requirements and inefficient, slow germination correlated with elevated resistance of spores to heat and with specific genetic features, indicating a common genetic basis of these three phenotypic traits. Clearly, interstrain variation and numerous factors that shape spore germination behavior challenge standardization of methods to recover highly heat-resistant spores from the environment and have an impact on the efficacy of preservation techniques used by the food industry to control spores.

scholarly journals Daptomycin versus Friulimicin B: In-Depth Profiling of Bacillus subtilis Cell Envelope Stress Responses

2009 ◽  
Vol 53 (4) ◽  
pp. 1619-1623 ◽  
Author(s):  
Tina Wecke ◽  
Daniela Zühlke ◽  
Ulrike Mäder ◽  
Sina Jordan ◽  
Birgit Voigt ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Stress Responses ◽  
Cell Envelope ◽  
Depth Profiling ◽  
Peptide Antibiotics ◽  
Two Component System ◽  
Genome Wide ◽  
Envelope Stress ◽  
Σ Factor ◽  
Stress Sensing

ABSTRACT The related lipo(depsi)peptide antibiotics daptomycin and friulimicin B show great potential in the treatment of multiply resistant gram-positive pathogens. Applying genome-wide in-depth expression profiling, we compared the respective stress responses of Bacillus subtilis. Both antibiotics target envelope integrity, based on the strong induction of extracytoplasmic function σ factor-dependent gene expression. The cell envelope stress-sensing two-component system LiaRS is exclusively and strongly induced by daptomycin, indicative of different mechanisms of action in the two compounds.

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