scholarly journals Swarmer cell development of the bacteriumProteus mirabilisrequires the conserved ECA biosynthesis gene,rffG

2017 ◽  
Author(s):  
Kristin Little ◽  
Murray J. Tipping ◽  
Karine A. Gibbs
Keyword(s):  
Cell Morphology ◽  
Stress Responses ◽  
Cell Elongation ◽  
Cell Envelope ◽  
Membrane Composition ◽  
Swarmer Cell ◽  
Enterobacterial Common Antigen ◽  
Envelope Stress ◽  
Open Question ◽  
Additional Role

AbstractIndividual cells of the bacteriumProteus mirabiliscan elongate up to 40-fold on surfaces before engaging in a cooperative surface-based motility termed swarming. How cells regulate this dramatic morphological remodeling remains an open question. In this paper, we move forward the understanding of this regulation by demonstrating thatP. mirabilisrequires the generffGfor swarmer cell elongation and subsequent swarm motility. TherffGgene encodes a protein homologous to the dTDP-glucose 4,6 dehydratase protein ofEscherichia coli, which contributes to Enterobacterial Common Antigen biosynthesis. Here we characterize therffGgene inP. mirabilis, demonstrating that it is required for the production of large lipopolysaccharide-linked moieties necessary for wild-type cell envelope integrity. We show that absence of therffGgene induces several stress-responsive pathways including those controlled by the transcriptional regulators RpoS, CaiF, and RcsB. We further show that inrffG-deficient cells, suppression of the Rcs phosphorelay, via loss of RcsB, is sufficient to induce cell elongation and swarm motility. However, loss of RcsB does not rescue cell envelope integrity defects and instead results in abnormally shaped cells, including cells producing more than two poles. We conclude that a RcsB-mediated response acts to suppress emergence of shape defects in cell envelope-compromised cells, suggesting an additional role for RcsB in maintaining cell morphology under stress conditions. We further propose that the composition of the cell envelope acts as a checkpoint before cells initiate swarmer cell elongation and motility.Importance statementP. mirabilisswarm motility has been implicated in pathogenesis. We have found that cells deploy multiple uncharacterized strategies to handle cell envelope stress beyond the Rcs phosphorelay when attempting to engage in swarm motility. While RcsB is known to directly inhibit the master transcriptional regulator for swarming, we have shown an additional role for RcsB in protecting cell morphology. These data support a growing appreciation that the Rcs phosphorelay is a multi-functional regulator of cell morphology in addition to its role in microbial stress responses. These data also strengthen the paradigm that outer membrane composition is a crucial checkpoint for modulating entry into swarm motility. Furthermore, therffG-dependent moieties provide a novel, attractive target for potential antimicrobials.

scholarly journals Swarmer Cell Development of the BacteriumProteus mirabilisRequires the Conserved Enterobacterial Common Antigen Biosynthesis GenerffG

2018 ◽  
Vol 200 (18) ◽  
Author(s):  
Kristin Little ◽  
Murray J. Tipping ◽  
Karine A. Gibbs
Keyword(s):  
Cell Morphology ◽  
Stress Responses ◽  
Proteus Mirabilis ◽  
Cell Elongation ◽  
Cell Envelope ◽  
Common Antigen ◽  
Swarmer Cell ◽  
Content Type ◽  
Enterobacterial Common Antigen ◽  
Additional Role

ABSTRACTIndividual cells of the bacteriumProteus mirabiliscan elongate up to 40-fold on surfaces before engaging in a cooperative surface-based motility termed swarming. How cells regulate this dramatic morphological remodeling remains an open question. In this paper, we move forward the understanding of this regulation by demonstrating thatP. mirabilisrequires the generffGfor swarmer cell elongation and subsequent swarm motility. TherffGgene encodes a protein homologous to the dTDP-glucose 4,6-dehydratase protein ofEscherichia coli, which contributes to enterobacterial common antigen biosynthesis. Here, we characterize therffGgene inP. mirabilis, demonstrating that it is required for the production of large lipopolysaccharide-linked moieties necessary for wild-type cell envelope integrity. We show that the absence of therffGgene induces several stress response pathways, including those controlled by the transcriptional regulators RpoS, CaiF, and RcsB. We further show that inrffG-deficient cells, the suppression of the Rcs phosphorelay, via loss of RcsB, is sufficient to induce cell elongation and swarm motility. However, the loss of RcsB does not rescue cell envelope integrity defects and instead results in abnormally shaped cells, including cells producing more than two poles. We conclude that an RcsB-mediated response acts to suppress the emergence of shape defects in cell envelope-compromised cells, suggesting an additional role for RcsB in maintaining cell morphology under stress conditions. We further propose that the composition of the cell envelope acts as a checkpoint before cells initiate swarmer cell elongation and motility.IMPORTANCEProteus mirabilisswarm motility has been implicated in pathogenesis. We have found that cells deploy multiple uncharacterized strategies to handle cell envelope stress beyond the Rcs phosphorelay when attempting to engage in swarm motility. While RcsB is known to directly inhibit the master transcriptional regulator for swarming, we have shown an additional role for RcsB in protecting cell morphology. These data support a growing appreciation that the Rcs phosphorelay is a multifunctional regulator of cell morphology in addition to its role in microbial stress responses. These data also strengthen the paradigm that outer membrane composition is a crucial checkpoint for modulating entry into swarm motility. Furthermore, therffG-dependent moieties provide a novel attractive target for potential antimicrobials.

scholarly journals Mini Review: Bacterial Membrane Composition and Its Modulation in Response to Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Jessica R. Willdigg ◽  
John D. Helmann
Keyword(s):  
Stress Responses ◽  
Membrane Structure ◽  
Cell Envelope ◽  
Model System ◽  
Clinical Settings ◽  
Bacterial Membrane ◽  
Membrane Composition ◽  
Cell Wall Synthesis ◽  
Envelope Stress ◽  
Response To Stress

Antibiotics and other agents that perturb the synthesis or integrity of the bacterial cell envelope trigger compensatory stress responses. Focusing on Bacillus subtilis as a model system, this mini-review summarizes current views of membrane structure and insights into how cell envelope stress responses remodel and protect the membrane. Altering the composition and properties of the membrane and its associated proteome can protect cells against detergents, antimicrobial peptides, and pore-forming compounds while also, indirectly, contributing to resistance against compounds that affect cell wall synthesis. Many of these regulatory responses are broadly conserved, even where the details of regulation may differ, and can be important in the emergence of antibiotic resistance in clinical settings.

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 Rcs Phosphorelay Is a Cell Envelope Stress Response Activated by Peptidoglycan Stress and Contributes to Intrinsic Antibiotic Resistance

2008 ◽  
Vol 190 (6) ◽  
pp. 2065-2074 ◽  
Author(s):  
Mary E. Laubacher ◽  
Sarah E. Ades
Keyword(s):  
Outer Membrane ◽  
Single Molecule ◽  
Stress Responses ◽  
Structural Integrity ◽  
Cell Envelope ◽  
Gram Negative Bacteria ◽  
Intrinsic Resistance ◽  
Gram Negative ◽  
Envelope Stress ◽  
Peptidoglycan Layer

ABSTRACTGram-negative bacteria possess stress responses to maintain the integrity of the cell envelope. Stress sensors monitor outer membrane permeability, envelope protein folding, and energization of the inner membrane. The systems used by gram-negative bacteria to sense and combat stress resulting from disruption of the peptidoglycan layer are not well characterized. The peptidoglycan layer is a single molecule that completely surrounds the cell and ensures its structural integrity. During cell growth, new peptidoglycan subunits are incorporated into the peptidoglycan layer by a series of enzymes called the penicillin-binding proteins (PBPs). To explore how gram-negative bacteria respond to peptidoglycan stress, global gene expression analysis was used to identifyEscherichia colistress responses activated following inhibition of specific PBPs by the β-lactam antibiotics amdinocillin (mecillinam) and cefsulodin. Inhibition of PBPs with different roles in peptidoglycan synthesis has different consequences for cell morphology and viability, suggesting that not all perturbations to the peptidoglycan layer generate equivalent stresses. We demonstrate that inhibition of different PBPs resulted in both shared and unique stress responses. The regulation of capsular synthesis (Rcs) phosphorelay was activated by inhibition of all PBPs tested. Furthermore, we show that activation of the Rcs phosphorelay increased survival in the presence of these antibiotics, independently of capsule synthesis. Both activation of the phosphorelay and survival required signal transduction via the outer membrane lipoprotein RcsF and the response regulator RcsB. We propose that the Rcs pathway responds to peptidoglycan damage and contributes to the intrinsic resistance ofE. colito β-lactam antibiotics.

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.

scholarly journals Appropriate Regulation of the σE-Dependent Envelope Stress Response Is Necessary To Maintain Cell Envelope Integrity and Stationary-Phase Survival in Escherichia coli

2017 ◽  
Vol 199 (12) ◽  
Author(s):  
Hervé Nicoloff ◽  
Saumya Gopalkrishnan ◽  
Sarah E. Ades
Keyword(s):  
Escherichia Coli ◽  
Stationary Phase ◽  
Outer Membrane ◽  
Stress Responses ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Point Mutations ◽  
Content Type ◽  
Envelope Stress ◽  
Outer Membrane Porins

ABSTRACT The alternative sigma factor σE is a key component of the Escherichia coli response to cell envelope stress and is required for viability even in the absence of stress. The activity of σE increases during entry into stationary phase, suggesting an important role for σE when nutrients are limiting. Elevated σE activity has been proposed to activate a pathway leading to the lysis of nonculturable cells that accumulate during early stationary phase. To better understand σE-directed cell lysis and the role of σE in stationary phase, we investigated the effects of elevated σE activity in cultures grown for 10 days. We demonstrate that high σE activity is lethal for all cells in stationary phase, not only those that are nonculturable. Spontaneous mutants with reduced σE activity, due primarily to point mutations in the region of σE that binds the −35 promoter motif, arise and take over cultures within 5 to 6 days after entry into stationary phase. High σE activity leads to large reductions in the levels of outer membrane porins and increased membrane permeability, indicating membrane defects. These defects can be counteracted and stationary-phase lethality delayed significantly by stabilizing membranes with Mg2+ and buffering the growth medium or by deleting the σE-dependent small RNAs (sRNAs) MicA, RybB, and MicL, which inhibit the expression of porins and Lpp. Expression of these sRNAs also reverses the loss of viability following depletion of σE activity. Our results demonstrate that appropriate regulation of σE activity, ensuring that it is neither too high nor too low, is critical for envelope integrity and cell viability. IMPORTANCE The Gram-negative cell envelope and cytoplasm differ significantly, and separate responses have evolved to combat stress in each compartment. An array of cell envelope stress responses exist, each of which is focused on different parts of the envelope. The σE response is conserved in many enterobacteria and is tuned to monitor pathways for the maturation and delivery of outer membrane porins, lipoproteins, and lipopolysaccharide to the outer membrane. The activity of σE is tightly regulated to match the production of σE regulon members to the needs of the cell. In E. coli, loss of σE results in lethality. Here we demonstrate that excessive σE activity is also lethal and results in decreased membrane integrity, the very phenotype the system is designed to prevent.

scholarly journals Stress Reduction, Bacterial Style

2017 ◽  
Vol 199 (20) ◽  
Author(s):  
Susan Gottesman
Keyword(s):  
Escherichia Coli ◽  
Stress Reduction ◽  
Stress Responses ◽  
Cell Envelope ◽  
Content Type ◽  
E Coli ◽  
Envelope Stress ◽  
Multiple Cell ◽  
As Stress ◽  
Sigma E

ABSTRACT Bacteria have robust responses to a variety of stresses. In particular, bacteria like Escherichia coli have multiple cell envelope stress responses, and generally we evaluate what these responses are doing by the repair systems they induce. However, probably at least as important in interpreting what is being sensed as stress are the genes that these stress systems downregulate, directly or indirectly. This is discussed here for the Cpx and sigma E systems of E. coli.

scholarly journals Stress Physiology of Lactic Acid Bacteria

2016 ◽  
Vol 80 (3) ◽  
pp. 837-890 ◽  
Author(s):  
Konstantinos Papadimitriou ◽  
Ángel Alegría ◽  
Peter A. Bron ◽  
Maria de Angelis ◽  
Marco Gobbetti ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Stress Responses ◽  
Defense Mechanisms ◽  
Food Industry ◽  
Cell Envelope ◽  
Stress Physiology ◽  
Content Type ◽  
Envelope Stress ◽  
Cell Energy

SUMMARYLactic acid bacteria (LAB) are important starter, commensal, or pathogenic microorganisms. The stress physiology of LAB has been studied in depth for over 2 decades, fueled mostly by the technological implications of LAB robustness in the food industry. Survival of probiotic LAB in the host and the potential relatedness of LAB virulence to their stress resilience have intensified interest in the field. Thus, a wealth of information concerning stress responses exists today for strains as diverse as starter (e.g.,Lactococcus lactis), probiotic (e.g., severalLactobacillusspp.), and pathogenic (e.g.,EnterococcusandStreptococcusspp.) LAB. Here we present the state of the art for LAB stress behavior. We describe the multitude of stresses that LAB are confronted with, and we present the experimental context used to study the stress responses of LAB, focusing on adaptation, habituation, and cross-protection as well as on self-induced multistress resistance in stationary phase, biofilms, and dormancy. We also consider stress responses at the population and single-cell levels. Subsequently, we concentrate on the stress defense mechanisms that have been reported to date, grouping them according to their direct participation in preserving cell energy, defending macromolecules, and protecting the cell envelope. Stress-induced responses of probiotic LAB and commensal/pathogenic LAB are highlighted separately due to the complexity of the peculiar multistress conditions to which these bacteria are subjected in their hosts. Induction of prophages under environmental stresses is then discussed. Finally, we present systems-based strategies to characterize the “stressome” of LAB and to engineer new food-related and probiotic LAB with improved stress tolerance.

scholarly journals The Periplasmic PDZ Domain–Containing Protein Prc Modulates Full Virulence, Envelops Stress Responses, and Directly Interacts with Dipeptidyl Peptidase of Xanthomonas oryzae pv. oryzae

2014 ◽  
Vol 27 (2) ◽  
pp. 101-112 ◽  
Author(s):  
Chao-Ying Deng ◽  
Ai-Hua Deng ◽  
Shu-Tao Sun ◽  
Li Wang ◽  
Jie Wu ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cell Envelope ◽  
Pdz Domain ◽  
Sodium Dodecylsulfate ◽  
Dipeptidyl Peptidase ◽  
Xanthomonas Oryzae ◽  
Bacterial Cells ◽  
Envelope Stress

PDZ domain–containing proteases, also known as HtrA family proteases, play important roles in bacterial cells by modulating disease pathogenesis and cell-envelope stress responses. These proteases have diverse functions through proteolysis- and nonproteolysis-dependent modes. Here, we report that the genome of the causative agent of rice bacterial blight, Xanthomonas oryzae pv. oryzae, encodes seven PDZ domain–containing proteins. Systematic inactivation of their encoding genes revealed that PXO_01122 and PXO_04290 (prc) are involved in virulence. prc encodes a putative HtrA family protease that localizes in the bacterial periplasm. Mutation of prc also resulted in susceptibility to multiple environmental stresses, including H2O2, sodium dodecylsulfate, and osmolarity stresses. Comparative subproteomic analyses showed that the amounts of 34 periplasmic proteins were lower in the prc mutant than in wild-type. These proteins were associated with proteolysis, biosynthesis of macromolecules, carbohydrate or energy metabolism, signal transduction, and protein translocation or folding. We provide in vivo and in vitro evidence demonstrating that Prc stabilizes and directly binds to one of these proteins, DppP, a dipeptidyl peptidase contributing to full virulence. Taken together, our results suggest that Prc contributes to bacterial virulence by acting as a periplasmic modulator of cell-envelope stress responses.

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