Intracellular Signaling by thecomRSSystem inStreptococcus mutansGenetic Competence

ABSTRACTEntry into genetic competence in streptococci is controlled by ComX, an alternative sigma factor for genes that enable the import of exogenous DNA. InStreptococcus mutans, the immediate activator ofcomXis the ComRS quorum system. ComS is the precursor of XIP, a seven-residue peptide that is imported into the cell and interacts with the cytosolic receptor ComR to form a transcriptional activator for bothcomXandcomS. Although intercellular quorum signaling by ComRS has been demonstrated, observations of bimodal expression ofcomXsuggest thatcomRSmay also function as an intracellular feedback loop, activatingcomXwithout export or detection of extracellular XIP. Here we used microfluidic and single-cell methods to test whether ComRS induction ofcomXrequires extracellular XIP or ComS. We found that individualcomS-overexpressing cells activate their owncomX, independently of the rate at which their growth medium is replaced. However, in the absence of lysis they do not activatecomS-deficient mutants growing in coculture. We also found that induction ofcomRandcomSgenes introduced intoEscherichia colicells leads to activation of acomXreporter. Therefore, ComRS control ofcomXdoes not require either the import or extracellular accumulation of ComS or XIP or specific processing of ComS to XIP. We also found that endogenously and exogenously produced ComS and XIP have inequivalent effects oncomXactivation. These data are fully consistent with identification of intracellular positive feedback incomStranscription as the origin of bimodalcomXexpression inS. mutans.IMPORTANCEThe ComRS system can function as a quorum sensing trigger for genetic competence inS. mutans. The signal peptide XIP, which is derived from the precursor ComS, enters the cell and interacts with the Rgg-type cytosolic receptor ComR to activatecomX, which encodes the alternative sigma factor for the late competence genes. Previous studies have demonstrated intercellular signaling via ComRS, although release of the ComS or XIP peptide to the extracellular medium appears to require lysis of the producing cells. Here we tested the complementary hypothesis that ComRS can drivecomXthrough a purely intracellular mechanism that does not depend on extracellular accumulation or import of ComS or XIP. By combining single-cell, coculture, and microfluidic approaches, we demonstrated that endogenously produced ComS can enable ComRS to activatecomXwithout requiring processing, export, or import. These data provide insight into intracellular mechanisms that generate noise and heterogeneity inS. mutanscompetence.

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Alternative Sigma Factor SigK Has a Role in Stress Tolerance of Group I Clostridium botulinum Strain ATCC 3502

Applied and Environmental Microbiology ◽

10.1128/aem.04036-12 ◽

2013 ◽

Vol 79 (12) ◽

pp. 3867-3869 ◽

Cited By ~ 12

Author(s):

Elias Dahlsten ◽

David Kirk ◽

Miia Lindström ◽

Hannu Korkeala

Keyword(s):

Stress Tolerance ◽

Sigma Factor ◽

Clostridium Botulinum ◽

Alternative Sigma Factor ◽

Strain Atcc ◽

Content Type ◽

Osmotic Stress Tolerance ◽

Group I ◽

Temperature Downshift

ABSTRACTThe role of the alternative sigma factor SigK in cold and osmotic stress tolerance ofClostridium botulinumATCC 3502 was demonstrated by induction ofsigKafter temperature downshift and exposure to hyperosmotic conditions and by impaired growth of thesigKmutants under the respective conditions.

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Listeria monocytogenes σHContributes to Expression of Competence Genes and Intracellular Growth

Journal of Bacteriology ◽

10.1128/jb.00718-15 ◽

2016 ◽

Vol 198 (8) ◽

pp. 1207-1217 ◽

Cited By ~ 4

Author(s):

Veronica Medrano Romero ◽

Kazuya Morikawa

Keyword(s):

Transcription Factor ◽

Listeria Monocytogenes ◽

Sigma Factor ◽

Physiological Role ◽

Population Level ◽

Alternative Sigma Factor ◽

Intracellular Growth ◽

Content Type ◽

Gram Positive Bacteria ◽

Regulation Scheme

ABSTRACTThe alternative sigma factor σHhas two functions in Gram-positive bacteria: it regulates sporulation and the development of genetic competence.Listeria monocytogenesis a nonsporulating species in which competence has not yet been detected. Nevertheless, the main competence regulators and a series of orthologous genes that form the competence machinery are present in its genome; some of the competence genes play a role in optimal phagosomal escape. In this study, strains overexpressing σHand strains with a σHdeletion were used to elucidate the contribution of σHto the expression of the competence machinery genes inL. monocytogenes. Gene expression analysis showed that σHis, indeed, involved incomGandcomEregulation. Unexpectedly, we observed a unique regulation scheme in which σHand the transcription factor ComK were involved. Population-level analysis showed that even with the overexpression of both factors, only a fraction of the cells expressed the competence machinery genes. Although we could not detect competence, σHwas crucial for phagosomal escape, which implies that this alternative sigma factor has specifically evolved to regulate theL. monocytogenesintracellular life cycle.IMPORTANCEListeria monocytogenescan be an intracellular pathogen capable of causing serious infections in humans and animal species. Recently, the competence machinery genes were described as being necessary for optimal phagosomal escape, in which the transcription factor ComK plays an important role. On the other hand, our previous phylogenetic analysis suggested that the alternative sigma factor σHmight play a role in the regulation of competence genes. The present study shows that some of the competence genes belong to the σHregulon and, importantly, that σHis essential for intracellular growth, implying a unique physiological role of σHamongFirmicutes.

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The Alternative Sigma Factor SigB Is Required for the Pathogenicity of Bacillus thuringiensis

Journal of Bacteriology ◽

10.1128/jb.00265-20 ◽

2020 ◽

Vol 202 (21) ◽

Author(s):

Stéphanie Henry ◽

Didier Lereclus ◽

Leyla Slamti

Keyword(s):

Life Cycle ◽

Stress Response ◽

Bacillus Thuringiensis ◽

Sigma Factor ◽

Oral Route ◽

Alternative Sigma Factor ◽

Gram Positive ◽

Content Type ◽

General Stress Response

ABSTRACT To adapt to changing and potentially hostile environments, bacteria can activate the transcription of genes under the control of alternative sigma factors, such as SigB, a master regulator of the general stress response in several Gram-positive species. Bacillus thuringiensis is a Gram-positive spore-forming invertebrate pathogen whose life cycle includes a variety of environments, including plants and the insect hemocoel or gut. Here, we assessed the role of SigB during the infectious cycle of B. thuringiensis in a Galleria mellonella insect model. We used a fluorescent reporter coupled to flow cytometry and showed that SigB was activated in vivo. We also showed that the pathogenicity of the ΔsigB mutant was severely affected when inoculated via the oral route, suggesting that SigB is critical for B. thuringiensis adaptation to the gut environment of the insect. We could not detect an effect of the sigB deletion on the survival of the bacteria or on their sporulation efficiency in the cadavers. However, the gene encoding the pleiotropic regulator Spo0A was upregulated in the ΔsigB mutant cells during the infectious process. IMPORTANCE Pathogenic bacteria often need to transition between different ecosystems, and their ability to cope with such variations is critical for their survival. Several Gram-positive species have developed an adaptive response mediated by the general stress response alternative sigma factor SigB. In order to understand the ecophysiological role of this regulator in Bacillus thuringiensis, an entomopathogenic bacterium widely used as a biopesticide, we sought to examine the fate of a ΔsigB mutant during its life cycle in the natural setting of an insect larva. This allowed us, in particular, to show that SigB was activated during infection and that it was required for the pathogenicity of B. thuringiensis via the oral route of infection.

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Salt-Induced Stress Stimulates a Lipoteichoic Acid-Specific Three-Component Glycosylation System inStaphylococcus aureus

Journal of Bacteriology ◽

10.1128/jb.00017-18 ◽

2018 ◽

Vol 200 (12) ◽

Cited By ~ 15

Author(s):

Kelvin Kho ◽

Timothy C. Meredith

Keyword(s):

Staphylococcus Aureus ◽

Sigma Factor ◽

Cell Envelope ◽

Normal Growth ◽

Lipoteichoic Acid ◽

Growth Conditions ◽

Growth Media ◽

Alternative Sigma Factor ◽

Content Type

ABSTRACTLipoteichoic acid (LTA) inStaphylococcus aureusis a poly-glycerophosphate polymer anchored to the outer surface of the cell membrane. LTA has numerous roles in cell envelope physiology, including regulating cell autolysis, coordinating cell division, and adapting to environmental growth conditions. LTA is often further modified with substituents, includingd-alanine and glycosyl groups, to alter cellular function. While the genetic determinants ofd-alanylation have been largely defined, the route of LTA glycosylation and its role in cell envelope physiology have remained unknown, in part due to the low levels of basal LTA glycosylation inS. aureus. We demonstrate here thatS. aureusutilizes a membrane-associated three-component glycosylation system composed of an undecaprenol (Und)N-acetylglucosamine (GlcNAc) charging enzyme (CsbB; SAOUHSC_00713), a putative flippase to transport loaded substrate to the outside surface of the cell (GtcA; SAOUHSC_02722), and finally an LTA-specific glycosyltransferase that adds α-GlcNAc moieties to LTA (YfhO; SAOUHSC_01213). We demonstrate that this system is specific for LTA with no cross recognition of the structurally similar polyribitol phosphate containing wall teichoic acids. We show that while wild-typeS. aureusLTA has only a trace of GlcNAcylated LTA under normal growth conditions, amounts are raised upon either overexpressing CsbB, reducing endogenousd-alanylation activity, expressing the cell envelope stress responsive alternative sigma factor SigB, or by exposure to environmental stress-inducing culture conditions, including growth media containing high levels of sodium chloride.IMPORTANCEThe role of glycosylation in the structure and function ofStaphylococcus aureuslipoteichoic acid (LTA) is largely unknown. By defining key components of the LTA three-component glycosylation pathway and uncovering stress-induced regulation by the alternative sigma factor SigB, the role ofN-acetylglucosamine tailoring during adaptation to environmental stresses can now be elucidated. As thedltand glycosylation pathways compete for the same sites on LTA and induction of glycosylation results in decreasedd-alanylation, the interplay between the two modification systems holds implications for resistance to antibiotics and antimicrobial peptides.

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DksA and ppGpp Regulate the σS Stress Response by Activating Promoters for the Small RNA DsrA and the Anti-Adapter Protein IraP

Journal of Bacteriology ◽

10.1128/jb.00463-17 ◽

2017 ◽

Vol 200 (2) ◽

Cited By ~ 17

Author(s):

Mary E. Girard ◽

Saumya Gopalkrishnan ◽

Elicia D. Grace ◽

Jennifer A. Halliday ◽

Richard L. Gourse ◽

...

Keyword(s):

Stress Response ◽

Rna Polymerase ◽

Stationary Phase ◽

Sigma Factor ◽

Bacterial Species ◽

Adaptor Protein ◽

Large Family ◽

Alternative Sigma Factor ◽

Term Survival ◽

Content Type

ABSTRACT σS is an alternative sigma factor, encoded by the rpoS gene, that redirects cellular transcription to a large family of genes in response to stressful environmental signals. This so-called σS general stress response is necessary for survival in many bacterial species and is controlled by a complex, multifactorial pathway that regulates σS levels transcriptionally, translationally, and posttranslationally in Escherichia coli. It was shown previously that the transcription factor DksA and its cofactor, ppGpp, are among the many factors governing σS synthesis, thus playing an important role in activation of the σS stress response. However, the mechanisms responsible for the effects of DksA and ppGpp have not been elucidated fully. We describe here how DksA and ppGpp directly activate the promoters for the anti-adaptor protein IraP and the small regulatory RNA DsrA, thereby indirectly influencing σS levels. In addition, based on effects of DksAN88I, a previously identified DksA variant with increased affinity for RNA polymerase (RNAP), we show that DksA can increase σS activity by another indirect mechanism. We propose that by reducing rRNA transcription, DksA and ppGpp increase the availability of core RNAP for binding to σS and also increase transcription from other promoters, including PdsrA and PiraP. By improving the translation and stabilization of σS, as well as the ability of other promoters to compete for RNAP, DksA and ppGpp contribute to the switch in the transcription program needed for stress adaptation. IMPORTANCE Bacteria spend relatively little time in log phase outside the optimized environment found in a laboratory. They have evolved to make the most of alternating feast and famine conditions by seamlessly transitioning between rapid growth and stationary phase, a lower metabolic mode that is crucial for long-term survival. One of the key regulators of the switch in gene expression that characterizes stationary phase is the alternative sigma factor σS. Understanding the factors governing σS activity is central to unraveling the complexities of growth, adaptation to stress, and pathogenesis. Here, we describe three mechanisms by which the RNA polymerase binding factor DksA and the second messenger ppGpp regulate σS levels.

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Threshold regulation and stochasticity from the MecA/ClpCP proteolytic system inStreptococcus mutanscompetence

10.1101/263210 ◽

2018 ◽

Author(s):

M. Son ◽

J. Kaspar ◽

S.J. Ahn ◽

R.A. Burne ◽

S.J. Hagen

Keyword(s):

Streptococcus Mutans ◽

Sigma Factor ◽

Phenotypic Diversity ◽

Bacterial Species ◽

Alternative Sigma Factor ◽

Cell Heterogeneity ◽

Proteolytic System ◽

Genetic Competence ◽

Threshold Control ◽

Low Levels

SummaryMany bacterial species use the MecA/ClpCP proteolytic system to block entry into genetic competence. InStreptococcus mutans, MecA/ClpCP degrades ComX (also called SigX), an alternative sigma factor for thecomYoperon and other late competence genes. Although the mechanism of MecA/ClpCP has been studied in multipleStreptococcusspecies, its role within noisy competence pathways is poorly understood.S. mutanscompetence can be triggered by two different peptides, CSP and XIP, but it is not known whether MecA/ClpCP acts similarly for both stimuli, how it affects competence heterogeneity, and how its regulation is overcome. We have studied the effect of MecA/ClpCP on the activation ofcomYin individualS. mutanscells. Our data show that MecA/ClpCP is active under both XIP and CSP stimulation, that it provides threshold control ofcomY, and that it adds noise incomYexpression. Our data agree quantitatively with a model in which MecA/ClpCP prevents adventitious entry into competence by sequestering or intercepting low levels of ComX. Competence is permitted when ComX levels exceed a threshold, but cell-to-cell heterogeneity in MecA levels creates variability in that threshold. Therefore MecA/ClpCP provides a stochastic switch, located downstream of the already noisycomX, that enhances phenotypic diversity.

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Redefining the Clostridioides difficile σB Regulon: σB Activates Genes Involved in Detoxifying Radicals That Can Result from the Exposure to Antimicrobials and Hydrogen Peroxide

mSphere ◽

10.1128/msphere.00728-20 ◽

2020 ◽

Vol 5 (5) ◽

Cited By ~ 1

Author(s):

Ilse M. Boekhoud ◽

Annika-Marisa Michel ◽

Jeroen Corver ◽

Dieter Jahn ◽

Wiep Klaas Smits

Keyword(s):

Hydrogen Peroxide ◽

Stress Response ◽

Sigma Factor ◽

Gene Activation ◽

Luciferase Reporter ◽

Alternative Sigma Factor ◽

Gram Positive ◽

Content Type ◽

Gram Positive Bacteria ◽

Sigma B

ABSTRACT In many Gram-positive bacteria, the general stress response is regulated at the transcriptional level by the alternative sigma factor sigma B (σB). In C. difficile, σB has been implicated in protection against stressors such as reactive oxygen species (ROS) and antimicrobial compounds. Here, we used an anti-σB antibody to demonstrate time-limited overproduction of σB in C. difficile despite its toxicity at higher cellular concentrations. This toxicity eventually led to the loss of the plasmid used for anhydrotetracycline-induced σB gene expression. Inducible σB overproduction uncouples σB expression from its native regulatory network and allows for the refinement of the previously proposed σB regulon. At least 32% of the regulon was found to consist of genes involved in the response to reactive radicals. Direct gene activation by C. difficile σB was demonstrated through in vitro runoff transcription of specific target genes (cd0350, cd3614, cd3605, and cd2963). Finally, we demonstrated that different antimicrobials and hydrogen peroxide induce these genes in a manner dependent on this sigma factor, using a plate-based luciferase reporter assay. Together, our work suggests that lethal exposure to antimicrobials may result in the formation of toxic radicals that lead to σB-dependent gene activation. IMPORTANCE Sigma B is the alternative sigma factor governing stress response in many Gram-positive bacteria. In C. difficile, a sigB mutant shows pleiotropic transcriptional effects. Here, we determine genes that are likely direct targets of σB by evaluating the transcriptional effects of σB overproduction, provide biochemical evidence of direct transcriptional activation by σB, and show that σB-dependent genes can be activated by antimicrobials. Together, our data suggest that σB is a key player in dealing with toxic radicals.

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Alternative Sigma Factor RpoX Is a Part of the RpoE Regulon and Plays Distinct Roles in Stress Responses, Motility, Biofilm Formation, and Hemolytic Activities in the Marine Pathogen Vibrio alginolyticus

Applied and Environmental Microbiology ◽

10.1128/aem.00234-19 ◽

2019 ◽

Vol 85 (14) ◽

Cited By ~ 3

Author(s):

Dan Gu ◽

Jun Zhang ◽

Yuan Hao ◽

Rongjing Xu ◽

Yuanxing Zhang ◽

...

Keyword(s):

High Temperature ◽

Osmotic Stress ◽

Stress Responses ◽

Sigma Factor ◽

Biofilm Formation ◽

Vibrio Alginolyticus ◽

Alternative Sigma Factor ◽

Rna Seq ◽

Content Type ◽

Regulatory Cascades

ABSTRACT Vibrio alginolyticus is one of the most abundant microorganisms in marine environments and is also an opportunistic pathogen mediating high-mortality vibriosis in marine animals. Alternative sigma factors play essential roles in bacterial pathogens in the adaptation to environmental changes during infection and the adaptation to various niches, but little is known about them for V. alginolyticus. Our previous investigation indicated that the transcript level of the gene rpoX significantly decreased in an RpoE mutant. Here, we found that rpoX was highly expressed in response to high temperature and low osmotic stress and was under the direct control of the alternative sigma factor RpoE and its own product RpoX. Moreover, transcriptome sequencing (RNA-seq) results showed that RpoE and RpoX had different regulons, although they coregulated 105 genes at high temperature (42°C), including genes associated with biofilm formation, motility, virulence, regulatory factors, and the stress response. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) analyses as well as electrophoretic mobility shift assays (EMSAs) revealed the distinct binding motifs of RpoE and RpoX proteins. Furthermore, quantitative real-time reverse transcription-PCR (qRT-PCR) analysis also confirmed that RpoX can upregulate genes associated with flagella, biofilm formation, and hemolytic activities at higher temperatures. rpoX abrogation does not appear to attenuate virulence toward model fish at normal temperature. Collectively, data from this study demonstrated the regulatory cascades of RpoE and an alternative sigma factor, RpoX, in response to heat and osmotic stresses and their distinct and overlapping roles in pathogenesis and stress responses in the marine bacterium V. alginolyticus. IMPORTANCE The alternative sigma factor RpoE is essential for the virulence of Vibrio alginolyticus toward marine fish, coral, and other animals in response to sea surface temperature increases. In this study, we characterized another alternative sigma factor, RpoX, which is induced at high temperatures and under low-osmotic-stress conditions. The expression of rpoX is under the tight control of RpoE and RpoX. Although RpoE and RpoX coregulate 105 genes, they are programming different regulatory functions in stress responses and virulence in V. alginolyticus. These findings illuminated the RpoE-RpoX-centered regulatory cascades and their distinct and overlapping regulatory roles in V. alginolyticus, which facilitates unraveling of the mechanisms by which the bacterium causes diseases in various sea animals in response to temperature fluctuations as well as the development of appropriate strategies to tackle infections by this bacterium.

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Genome-Scale Mapping Reveals Complex Regulatory Activities of RpoN in Yersinia pseudotuberculosis

mSystems ◽

10.1128/msystems.01006-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

A. K. M. Firoj Mahmud ◽

Kristina Nilsson ◽

Anna Fahlgren ◽

Roberto Navais ◽

Rajdeep Choudhury ◽

...

Keyword(s):

Gene Expression ◽

Binding Sites ◽

Sigma Factor ◽

Biofilm Formation ◽

Yersinia Pseudotuberculosis ◽

Binding Motif ◽

Alternative Sigma Factor ◽

Altered Expression ◽

Content Type ◽

Sense Strand

ABSTRACT RpoN, an alternative sigma factor commonly known as σ54, is implicated in persistent stages of Yersinia pseudotuberculosis infections in which genes associated with this regulator are upregulated. We here combined phenotypic and genomic assays to provide insight into its role and function in this pathogen. RpoN was found essential for Y. pseudotuberculosis virulence in mice, and in vitro functional assays showed that it controls biofilm formation and motility. Mapping genome-wide associations of Y. pseudotuberculosis RpoN using chromatin immunoprecipitation coupled with next-generation sequencing identified an RpoN binding motif located at 103 inter- and intragenic sites on both sense and antisense strands. Deletion of rpoN had a large impact on gene expression, including downregulation of genes encoding proteins involved in flagellar assembly, chemotaxis, and quorum sensing. There were also clear indications of cross talk with other sigma factors, together with indirect effects due to altered expression of other regulators. Matching differential gene expression with locations of the binding sites implicated around 130 genes or operons potentially activated or repressed by RpoN. Mutagenesis of selected intergenic binding sites confirmed both positive and negative regulatory effects of RpoN binding. Corresponding mutations of intragenic sense sites had less impact on associated gene expression. Surprisingly, mutating intragenic sites on the antisense strand commonly reduced expression of genes carried by the corresponding sense strand. IMPORTANCE The alternative sigma factor RpoN (σ54), which is widely distributed in eubacteria, has been implicated in controlling gene expression of importance for numerous functions including virulence. Proper responses to host environments are crucial for bacteria to establish infection, and regulatory mechanisms involved are therefore of high interest for development of future therapeutics. Little is known about the function of RpoN in the intestinal pathogen Y. pseudotuberculosis, and we therefore investigated its regulatory role in this pathogen. This regulator was indeed found to be critical for establishment of infection in mice, likely involving its requirement for motility and biofilm formation. The RpoN regulon involved both activating and suppressive effects on gene expression which could be confirmed with mutagenesis of identified binding sites. This is the first study of its kind of RpoN in Y. pseudotuberculosis, revealing complex regulation of gene expression involving both productive and silent effects of its binding to DNA, providing important information about RpoN regulation in enterobacteria.

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The Listeria monocytogenes σB Regulon and Its Virulence-Associated Functions Are Inhibited by a Small Molecule

mBio ◽

10.1128/mbio.00241-11 ◽

2011 ◽

Vol 2 (6) ◽

Cited By ~ 27

Author(s):

M. Elizabeth Palmer ◽

Soraya Chaturongakul ◽

Martin Wiedmann ◽

Kathryn J. Boor

Keyword(s):

Bacillus Subtilis ◽

Listeria Monocytogenes ◽

Small Molecule ◽

Sigma Factor ◽

Pathogen Transmission ◽

Bile Salt Hydrolase ◽

Alternative Sigma Factor ◽

Bacterial Survival ◽

Gram Positive ◽

Content Type

ABSTRACTThe stress-responsive alternative sigma factor σBis conserved across diverse Gram-positive bacterial genera. InListeria monocytogenes, σBregulates transcription of >150 genes, including genes contributing to virulence and to bacterial survival under host-associated stress conditions, such as those encountered in the human gastrointestinal lumen. An inhibitor ofL. monocytogenesσBactivity was identified by screening ~57,000 natural and synthesized small molecules using a high-throughput cell-based assay. The compound fluoro-phenyl-styrene-sulfonamide (FPSS) (IC50= 3.5 µM) downregulated the majority of genes previously identified as members of the σBregulon inL. monocytogenes10403S, thus generating a transcriptional profile comparable to that of a 10403S ΔsigBstrain. Specifically, of the 208 genes downregulated by FPSS, 75% had been identified previously as positively regulated by σB. Downregulated genes included key virulence and stress response genes, such asinlA,inlB,bsh,hfq,opuC, andbilE. From a functional perspective, FPSS also inhibitedL. monocytogenesinvasion of human intestinal epithelial cells and bile salt hydrolase activity. The ability of FPSS to inhibit σBactivity in bothL. monocytogenesandBacillus subtilisindicates its utility as a specific inhibitor of σBacross multiple Gram-positive genera.IMPORTANCEThe σBtranscription factor regulates expression of genes responsible for bacterial survival under changing environmental conditions and for virulence; therefore, this alternative sigma factor is important for transmission ofL. monocytogenesand other Gram-positive bacteria. Regulation of σBactivity is complex and tightly controlled, reflecting the key role of this factor in bacterial metabolism. We present multiple lines of evidence indicating that fluoro-phenyl-styrene-sulfonamide (FPSS) specifically inhibits activity of σBacross Gram-positive bacterial genera, i.e., in bothListeria monocytogenesandBacillus subtilis. Therefore, FPSS is an important new tool that will enable novel approaches for exploring complex regulatory networks inL. monocytogenesand other Gram-positive pathogens and for investigating small-molecule applications for controlling pathogen transmission.

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