scholarly journals In-Depth Profiling of the LiaR Response of Bacillus subtilis

2010 ◽  
Vol 192 (18) ◽  
pp. 4680-4693 ◽  
Author(s):  
Diana Wolf ◽  
Falk Kalamorz ◽  
Tina Wecke ◽  
Anna Juszczak ◽  
Ulrike Mäder ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Cell Envelope ◽  
Depth Profiling ◽  
Envelope Stress ◽  
Comprehensive Picture ◽  
A Cell ◽  
Gene Expression Studies ◽  
The Liar

ABSTRACT The Lia system, a cell envelope stress response module of Bacillus subtilis, is comprised of the LiaRS two-component system and a membrane-anchored inhibitor protein, LiaF. It is highly conserved in the Firmicutes bacteria, and all orthologs investigated so far are activated by cell wall antibiotics. In response to envelope stress, the systems in Firmicutes cocci induce the expression of a number of genes that are involved in conferring resistance against its inducers. In contrast, a complete picture of the LiaR regulon of B. subtilis is still missing and no phenotypes could be associated with mutants lacking LiaRS. Here, we performed genome-wide transcriptomic, proteomic, and in-depth phenotypic profiling of constitutive “Lia ON” and “Lia OFF” mutants to obtain a comprehensive picture of the Lia response of Bacillus subtilis. In addition to the known targets liaIH and yhcYZ-yhdA, we identified ydhE as a novel gene affected by LiaR-dependent regulation. The results of detailed follow-up gene expression studies, together with proteomic analysis, demonstrate that the liaIH operon represents the only relevant LiaR target locus in vivo. It encodes a small membrane protein (LiaI) and a phage shock protein homolog (LiaH). LiaH forms large oligomeric rings reminiscent of those described for Escherichia coli PspA or Arabidopsis thaliana Vipp1. The results of comprehensive phenotype studies demonstrated that the gene products of the liaIH operon are involved in protecting the cell against oxidative stress and some cell wall antibiotics. Our data suggest that the LiaFSR system of B. subtilis and, presumably, other Firmicutes bacilli coordinates a phage shock protein-like response.

scholarly journals An Antibiotic-Inducible Cell Wall-Associated Protein That Protects Bacillus subtilis from Autolysis

2007 ◽  
Vol 189 (13) ◽  
pp. 4671-4680 ◽  
Author(s):  
Letal I. Salzberg ◽  
John D. Helmann
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Cell Envelope ◽  
Sequence Similarity ◽  
Envelope Stress ◽  
Class B ◽  
Dependent Cell ◽  
A Cell ◽  
Close Relatives ◽  
Minimal Region

ABSTRACT In Bacillus subtilis, antibiotics that impair cell wall synthesis induce a characteristic stress response including the σW and σM regulons and the previously uncharacterized yoeB gene. Here we demonstrate that YoeB is a cell wall-associated protein with weak sequence similarity to a noncatalytic domain of class B penicillin-binding proteins. A yoeB-null mutant exhibits an increased rate of autolysis in response to cell wall-targeting antibiotics or nutrient depletion. This phenotype does not appear to be correlated with gross alterations in peptidoglycan structure or levels of autolysins. Promoter dissection experiments define a minimal region necessary for antibiotic-mediated induction of yoeB, and this region is highly conserved preceding yoeB homologs in close relatives of B. subtilis. These results support a model in which induction of YoeB in response to cell envelope stress decreases the activity of autolysins and thereby reduces the rate of antibiotic-dependent cell death.

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 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 Cell Envelope Stress Response in Cell Wall-Deficient L-Forms of Bacillus subtilis

2012 ◽  
Vol 56 (11) ◽  
pp. 5907-5915 ◽  
Author(s):  
Diana Wolf ◽  
Patricia Domínguez-Cuevas ◽  
Richard A. Daniel ◽  
Thorsten Mascher
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Culture Conditions ◽  
Content Type ◽  
Damage Sensing ◽  
Controlled Switching ◽  
Gene Assay ◽  
Envelope Stress

ABSTRACTL-forms are cell wall-deficient bacteria that can grow and proliferate in osmotically stabilizing media. Recently, a strain of the Gram-positive model bacteriumBacillus subtiliswas constructed that allowed controlled switching between rod-shaped wild-type cells and corresponding L-forms. Both states can be stably maintained under suitable culture conditions. Because of the absence of a cell wall, L-forms are known to be insensitive to β-lactam antibiotics, but reports on the susceptibility of L-forms to other antibiotics that interfere with membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and strongly influenced by strain background and method of L-form generation. Here we investigated the response ofB. subtilisto the presence of cell envelope antibiotics, with regard to both antibiotic resistance and the induction of the known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results show thatB. subtilisL-forms are resistant to antibiotics that interfere with the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are hypersensitive to nisin and daptomycin, which both affect membrane integrity. Moreover, we established alacZ-based reporter gene assay for L-forms and provide evidence that LiaRS senses its inducers indirectly (damage sensing), while the Bce module detects its inducers directly (drug sensing).

scholarly journals The yydFGHIJ Operon of Bacillus subtilis Encodes a Peptide That Induces the LiaRS Two-Component System

2007 ◽  
Vol 189 (23) ◽  
pp. 8616-8625 ◽  
Author(s):  
Bronwyn G. Butcher ◽  
Yi-Pin Lin ◽  
John D. Helmann
Keyword(s):  
Bacillus Subtilis ◽  
Cell Envelope ◽  
Negative Regulator ◽  
Two Component System ◽  
Sequence Comparisons ◽  
Component System ◽  
Amino Acid Peptide ◽  
Envelope Stress ◽  
Two Component ◽  
The Liar

ABSTRACT The Bacillus subtilis LiaRS two-component system (TCS) responds to perturbations of the cell envelope induced by lipid II-interacting antibiotics, such as vancomycin, ramoplanin, nisin, and bacitracin. Here, we characterize Tn7-generated mutations that induce the liaRS TCS. In addition to insertions in liaF, a known negative regulator of the LiaRS TCS, we identified two disruptions in the last two genes of the yydFGHIJ operon. This operon is predicted to encode a 49-amino-acid peptide (YydF), a modification enzyme (YydG), a membrane-embedded protease (YydH), and an ATP-binding cassette (ABC) transporter (YydIJ). Genome sequence comparisons suggest that the yydFGHIJ operon may have been acquired by horizontal transfer. Inactivation of the YydIJ transporter resulted in increased expression from the LiaR-dependent P liaI promoter only in the presence of the yydFGH genes. Cells harboring the complete yydFGHIJ operon induced LiaR activity in cocultured cells lacking either this transporter or the complete operon. These results suggest that this operon is involved in the synthesis and export of a modified peptide (YydF*) that elicits cell envelope stress sensed by the LiaRS TCS.

scholarly journals The Putative Lactococcal Extracytoplasmic Function Anti-Sigma Factor Llmg2447 Determines Resistance to the Cell Wall-Active Bacteriocin Lcn972

2012 ◽  
Vol 56 (11) ◽  
pp. 5520-5527 ◽  
Author(s):  
Clara Roces ◽  
Verónica Pérez ◽  
Ana B. Campelo ◽  
Diego Blanco ◽  
Jan Kok ◽  
...  
Keyword(s):  
Cell Wall ◽  
Sigma Factor ◽  
Cell Envelope ◽  
Cross Resistance ◽  
Penicillin Binding Protein ◽  
Insertion Element ◽  
Content Type ◽  
Envelope Stress ◽  
A Cell ◽  
Upregulated Genes

ABSTRACTLactococcin 972 (Lcn972) is a cell wall-active bacteriocin that inhibits cell wall biosynthesis inLactococcus lactis. In this work, the transcriptomes of the Lcn972-resistant (Lcnr) mutantL. lactisD1 and its parent strain were compared to identify factors involved in Lcn972 resistance. Upregulated genes included members of the cell envelope stress (CesSR) regulon, the penicillin-binding proteinpbpXgene and genellmg2447, which may encode a putative extracytoplasmic function (ECF) anti-sigma factor. The genellmg2447is located downstream of the nonfunctional ECF genesigXpseudo. Nisin-controlled expression ofllmg2447led to high Lcn972 resistance inL. lactis, with no cross-resistance to other cell wall-active antimicrobials. Upregulation ofllmg2447inL. lactisD1 (Lcnr) was linked to the integration of insertion element IS981into thellmg2447promoter region, replacing the native −35 box and activating the otherwise silent promoter P2447. This is the first example of an orphan ECF anti-sigma factor involved in bacteriocin resistance. This new role in neutralizing cell wall-active compounds (e.g., Lcn972) could have evolved from a putative primary function of Llmg2447 in sensing cell envelope stress.

scholarly journals L-form bacteria, cell walls and the origins of life

Open Biology ◽  
2013 ◽  
Vol 3 (1) ◽  
pp. 120143 ◽  
Author(s):  
Jeff Errington
Keyword(s):  
Cell Wall ◽  
Cell Envelope ◽  
Evolutionary Development ◽  
Last Common Ancestor ◽  
Bacterial Cells ◽  
A Cell ◽  
Evolutionary Radiations ◽  
Key Steps ◽  
Bacterial Domain

The peptidoglycan wall is a defining feature of bacterial cells and was probably already present in their last common ancestor. L-forms are bacterial variants that lack a cell wall and divide by a variety of processes involving membrane blebbing, tubulation, vesiculation and fission. Their unusual mode of proliferation provides a model for primitive cells and is reminiscent of recently developed in vitro vesicle reproduction processes. Invention of the cell wall may have underpinned the explosion of bacterial life on the Earth. Later innovations in cell envelope structure, particularly the emergence of the outer membrane of Gram-negative bacteria, possibly in an early endospore former, seem to have spurned further major evolutionary radiations. Comparative studies of bacterial cell envelope structure may help to resolve the early key steps in evolutionary development of the bacterial domain of life.

scholarly journals Insights into the role of lipoteichoic acids in Bacillus subtilis- a new function for MprF

2021 ◽  
Author(s):  
Aurelie Guyet ◽  
Amirah Alofi ◽  
Richard A Daniel
Keyword(s):  
Bacillus Subtilis ◽  
Cell Envelope ◽  
Cellular Level ◽  
Penicillin Binding Proteins ◽  
Class A ◽  
Peptidoglycan Synthesis ◽  
A Cell ◽  
Antimicrobial Peptide Resistance ◽  
Lipoteichoic Acids

In Bacillus subtilis, the cell is protected from the environment by a cell envelope, which comprises of layers of peptidoglycan that maintain the cell shape and anionic teichoic acids polymers whose biological function remains unclear. In B. subtilis, loss of all Class A Penicillin-Binding Proteins (aPBPs) which function in peptidoglycan synthesis is conditionally lethal. Here we show that this lethality is associated with an alteration of the lipoteichoic acids (LTA) and the accumulation of the major autolysin LytE in the cell wall. We provide the first evidence that the length and abundance of LTA acts to regulate the cellular level of LytE. Importantly, we identify a novel function for the aminoacyl-phosphatidylglycerol synthase MprF which acts to modulate LTA biosynthesis in B. subtilis and in the pathogen Staphylococcus aureus. This finding has implications for our understanding of antimicrobial peptide resistance (particularly daptomycin) in clinically relevant bacteria and MprF-associated virulence in pathogens, such as methicillin resistant S. aureus.

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.

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