scholarly journals The LiaFSR System Regulates the Cell Envelope Stress Response in Streptococcus mutans

2009 ◽  
Vol 191 (9) ◽  
pp. 2973-2984 ◽  
Author(s):  
Prashanth Suntharalingam ◽  
M. D. Senadheera ◽  
Richard W. Mair ◽  
Céline M. Lévesque ◽  
Dennis G. Cvitkovitch
Keyword(s):  
Stress Response ◽  
Streptococcus Mutans ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Transcriptional Analysis ◽  
Dependent Manner ◽  
Bacterial Survival ◽  
Concentration Dependent Manner ◽  
Lipid Ii ◽  
Envelope Stress

ABSTRACT Maintaining cell envelope integrity is critical for bacterial survival, including bacteria living in a complex and dynamic environment such as the human oral cavity. Streptococcus mutans, a major etiological agent of dental caries, uses two-component signal transduction systems (TCSTSs) to monitor and respond to various environmental stimuli. Previous studies have shown that the LiaSR TCSTS in S. mutans regulates virulence traits such as acid tolerance and biofilm formation. Although not examined in streptococci, homologs of LiaSR are widely disseminated in Firmicutes and function as part of the cell envelope stress response network. We describe here liaSR and its upstream liaF gene in the cell envelope stress tolerance of S. mutans strain UA159. Transcriptional analysis established liaSR as part of the pentacistronic liaFSR-ppiB-pnpB operon. A survey of cell envelope antimicrobials revealed that mutants deficient in one or all of the liaFSR genes were susceptible to Lipid II cycle interfering antibiotics and to chemicals that perturbed the cell membrane integrity. These compounds induced liaR transcription in a concentration-dependent manner. Notably, under bacitracin stress conditions, the LiaFSR signaling system was shown to induce transcription of several genes involved in membrane protein synthesis, peptidoglycan biosynthesis, envelope chaperone/proteases, and transcriptional regulators. In the absence of an inducer such as bacitracin, LiaF repressed LiaR-regulated expression, whereas supplementing cultures with bacitracin resulted in derepression of liaSR. While LiaF appears to be an integral component of the LiaSR signaling cascade, taken collectively, we report a novel role for LiaFSR in sensing cell envelope stress and preserving envelope integrity in S. mutans.

scholarly journals The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 729
Author(s):  
Angelika Diehl ◽  
Thomas M. Wood ◽  
Susanne Gebhard ◽  
Nathaniel I. Martin ◽  
Georg Fritz
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Stress Response ◽  
Cell Envelope ◽  
Resistance Mechanisms ◽  
Detailed Knowledge ◽  
Knock Out ◽  
Lipid Ii ◽  
Envelope Stress ◽  
The Impact

Cell wall antibiotics are important tools in our fight against Gram-positive pathogens, but many strains become increasingly resistant against existing drugs. Laspartomycin C is a novel antibiotic that targets undecaprenyl phosphate (UP), a key intermediate in the lipid II cycle of cell wall biosynthesis. While laspartomycin C has been thoroughly examined biochemically, detailed knowledge about potential resistance mechanisms in bacteria is lacking. Here, we use reporter strains to monitor the activity of central resistance modules in the Bacillus subtilis cell envelope stress response network during laspartomycin C attack and determine the impact on the resistance of these modules using knock-out strains. In contrast to the closely related UP-binding antibiotic friulimicin B, which only activates ECF σ factor-controlled stress response modules, we find that laspartomycin C additionally triggers activation of stress response systems reacting to membrane perturbation and blockage of other lipid II cycle intermediates. Interestingly, none of the studied resistance genes conferred any kind of protection against laspartomycin C. While this appears promising for therapeutic use of laspartomycin C, it raises concerns that existing cell envelope stress response networks may already be poised for spontaneous development of resistance during prolonged or repeated exposure to this new antibiotic.

scholarly journals Regulation of Flagellum Biosynthesis in Response to Cell Envelope Stress inSalmonella entericaSerovar Typhimurium

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Imke Spöring ◽  
Sebastian Felgner ◽  
Matthias Preuße ◽  
Denitsa Eckweiler ◽  
Manfred Rohde ◽  
...  
Keyword(s):  
Immune System ◽  
Stress Response ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Flagellar Biosynthesis ◽  
Envelope Stress ◽  
Flagellum Biosynthesis ◽  
Hostile Environments ◽  
Prime Target

ABSTRACTFlagellum-driven motility ofSalmonella entericaserovar Typhimurium facilitates host colonization. However, the large extracellular flagellum is also a prime target for the immune system. As consequence, expression of flagella is bistable within a population ofSalmonella, resulting in flagellated and nonflagellated subpopulations. This allows the bacteria to maximize fitness in hostile environments. The degenerate EAL domain protein RflP (formerly YdiV) is responsible for the bistable expression of flagella by directing the flagellar master regulatory complex FlhD4C2with respect to proteolytic degradation. Information concerning the environmental cues controlling expression ofrflPand thus about the bistable flagellar biosynthesis remains ambiguous. Here, we demonstrated that RflP responds to cell envelope stress and alterations of outer membrane integrity. Lipopolysaccharide (LPS) truncation mutants ofSalmonellaTyphimurium exhibited increasing motility defects due to downregulation of flagellar gene expression. Transposon mutagenesis and genetic profiling revealed that σ24(RpoE) and Rcs phosphorelay-dependent cell envelope stress response systems sense modifications of the lipopolysaccaride, low pH, and activity of the complement system. This subsequently results in activation of RflP expression and degradation of FlhD4C2via ClpXP. We speculate that the presence of diverse hostile environments inside the host might result in cell envelope damage and would thus trigger the repression of resource-costly and immunogenic flagellum biosynthesis via activation of the cell envelope stress response.IMPORTANCEPathogenic bacteria such asSalmonellaTyphimurium sense and adapt to a multitude of changing and stressful environments during host infection. At the initial stage of gastrointestinal colonization,Salmonellauses flagellum-mediated motility to reach preferred sites of infection. However, the flagellum also constitutes a prime target for the host’s immune response. Accordingly, the pathogen needs to determine the spatiotemporal stage of infection and control flagellar biosynthesis in a robust manner. We found thatSalmonellauses signals from cell envelope stress-sensing systems to turn off production of flagella. We speculate that downregulation of flagellum synthesis after cell envelope damage in hostile environments aids survival ofSalmonelladuring late stages of infection and provides a means to escape recognition by the immune system.

scholarly journals The BceABRS Four-Component System Regulates the Bacitracin-Induced Cell Envelope Stress Response in Streptococcus mutans

2010 ◽  
Vol 54 (9) ◽  
pp. 3895-3906 ◽  
Author(s):  
Jing Ouyang ◽  
Xiao-Lin Tian ◽  
Jennifer Versey ◽  
Alexander Wishart ◽  
Yung-Hua Li
Keyword(s):  
Stress Response ◽  
Streptococcus Mutans ◽  
Transcriptional Control ◽  
Cell Envelope ◽  
Genetic Locus ◽  
Binding Motif ◽  
Two Component System ◽  
Component System ◽  
Envelope Stress ◽  
Two Component

ABSTRACT Streptococcus mutans is known to be resistant to bacitracin, a cyclic polypeptide antibiotic produced by certain species of the genus Bacillus. This property is often exploited in the isolation of S. mutans strains from highly heterogeneous oral microflora. A genetic locus consisting of a four-gene operon, bceABRS (formerly mbrABCD), the component genes of which are homologous to Bacillus subtilis bceRS-bceAB (encoding a two-component system and an ABC transporter), is required for bacitracin resistance in S. mutans. Here we describe the identification of a DNA binding site for the BceR response regulator and its transcriptional control of the bceABRS operon in response to the presence of bacitracin. We provide evidence indicating that phosphorylated BceR binds directly to a conserved invert repeat located between bp −120 and −78 of the bceABRS promoter region and positively regulates expression of the bceABRS operon. We also demonstrate that sensing of bacitracin by the BceS histidine kinase requires the presence of an intact BceAB transporter, since deletion of either bceA or bceB abolishes BceRS-mediated bacitracin sensing. The results suggest that the BceAB transporter acts as a cosensor, together with the BceRS two-component system, for bacitracin perception in S. mutans. By searching the S. mutans genome databases, we have identified three additional genes that share the consensus BceR binding motif at their promoter regions. Our initial work has confirmed that expression of these genes is directly controlled by BceRS, indicating that the bceABRS operon, along with the three additional genes, forms the BceRS regulon in S. mutans. Taking these findings together, we conclude that BceABRS comprises a four-component system that plays an important role in stimulus sensing, signal transduction, the gene regulatory network, and substrate transport for the cell envelope stress response in S. mutans.

scholarly journals BrpA Is Involved in Regulation of Cell Envelope Stress Responses in Streptococcus mutans

2012 ◽  
Vol 78 (8) ◽  
pp. 2914-2922 ◽  
Author(s):  
J. P. Bitoun ◽  
S. Liao ◽  
X. Yao ◽  
S.-J. Ahn ◽  
R. Isoda ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Stress Responses ◽  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Cell Envelope ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Content Type ◽  
Lipid Ii ◽  
The Impact

ABSTRACTPrevious studies have shown that BrpA plays a major role in acid and oxidative stress tolerance and biofilm formation byStreptococcus mutans. Mutant strains lacking BrpA also display increased autolysis and decreased viability, suggesting a role for BrpA in cell envelope integrity. In this study, we examined the impact of BrpA deficiency on cell envelope stresses induced by envelope-active antimicrobials. Compared to the wild-type strain UA159, the BrpA-deficient mutant (TW14D) was significantly more susceptible to antimicrobial agents, especially lipid II inhibitors. Several genes involved in peptidoglycan synthesis were identified by DNA microarray analysis as downregulated in TW14D. Luciferase reporter gene fusion assays also revealed that expression ofbrpAis regulated in response to environmental conditions and stresses induced by exposure to subinhibitory concentrations of cell envelope antimicrobials. In aGalleria mellonella(wax worm) model, BrpA deficiency was shown to diminish the virulence ofS. mutansOMZ175, which, unlikeS. mutansUA159, efficiently kills the worms. Collectively, these results suggest that BrpA plays a role in the regulation of cell envelope integrity and that deficiency of BrpA adversely affects the fitness and diminishes the virulence of OMZ175, a highly invasive strain ofS. mutans.

scholarly journals Phyletic distribution and diversification of the Phage Shock Protein stress response system in bacteria and archaea

2021 ◽  
Author(s):  
Philipp F. Popp ◽  
Vadim M. Gumerov ◽  
Ekaterina P. Andrianova ◽  
Lisa Bewersdorf ◽  
Thorsten Mascher ◽  
...  
Keyword(s):  
Stress Response ◽  
Large Scale ◽  
Cell Envelope ◽  
Model Organisms ◽  
Microbial World ◽  
Natural Classification ◽  
Response System ◽  
Core Proteins ◽  
Envelope Stress

AbstractThe bacterial cell envelope is an essential structure that protects the cell from environmental threats, while simultaneously serving as communication interface and diffusion barrier. Therefore, maintaining cell envelope integrity is of vital importance for all microorganisms. Not surprisingly, evolution has shaped conserved protection networks that connect stress perception, transmembrane signal transduction and mediation of cellular responses upon cell envelope stress. The phage shock protein (PSP) stress response is one of such conserved protection networks. Most of the knowledge about the Psp response comes from studies in the Gram-negative model bacterium, Escherichia coli where the Psp system consists of several well-defined protein components. Homologous systems were identified in representatives of Proteobacteria, Actinobacteria, and Firmicutes; however, the Psp system distribution in the microbial world remains largely unknown. By carrying out a large-scale, unbiased comparative genomics analysis, we found components of the Psp system in many bacterial and archaeal phyla and demonstrated that the PSP system deviates dramatically from the proteobacterial prototype. Two of its core proteins, PspA and PspC, have been integrated in various (often phylum-specifically) conserved protein networks during evolution. Based on protein sequence and gene neighborhood analyses of pspA and pspC homologs, we built a natural classification system of PSP networks in bacteria and archaea. We performed a comprehensive in vivo protein interaction screen for the PSP network newly identified in the Gram-positive model organism Bacillus subtilis and found a strong interconnected PSP response system, illustrating the validity of our approach. Our study highlights the diversity of PSP organization and function across many bacterial and archaeal phyla and will serve as foundation for future studies of this envelope stress response beyond model organisms.

scholarly journals The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiao Meng ◽  
Glenn Young ◽  
Jingyu Chen
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Regulatory System ◽  
Virulence Regulation ◽  
Bacterial Interaction ◽  
Envelope Stress

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.

scholarly journals The three-component system EsrISR regulates a cell envelope stress response inCorynebacterium glutamicum

2017 ◽  
Vol 106 (5) ◽  
pp. 719-741 ◽  
Author(s):  
Britta Kleine ◽  
Ava Chattopadhyay ◽  
Tino Polen ◽  
Daniela Pinto ◽  
Thorsten Mascher ◽  
...  
Keyword(s):  
Stress Response ◽  
Cell Envelope ◽  
Component System ◽  
Envelope Stress ◽  
A Cell

scholarly journals Streptococcus mutans SpxA2 relays the signal of cell envelope stress from LiaR to effectors that maintain cell wall and membrane homeostasis

2020 ◽  
Vol 35 (3) ◽  
pp. 118-128
Author(s):  
Jonathon L. Baker ◽  
Sarah Saputo ◽  
Roberta C. Faustoferri ◽  
Robert G. Quivey
Keyword(s):  
Cell Wall ◽  
Streptococcus Mutans ◽  
Cell Envelope ◽  
Envelope Stress
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