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 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 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 Rod Shape Determination by the Bacillus subtilis Class B Penicillin-Binding Proteins Encoded by pbpA and pbpH

2003 ◽  
Vol 185 (16) ◽  
pp. 4717-4726 ◽  
Author(s):  
Yuping Wei ◽  
Teresa Havasy ◽  
Derrell C. McPherson ◽  
David L. Popham
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Binding Proteins ◽  
Structural Integrity ◽  
Sequence Similarity ◽  
Inducible Promoter ◽  
Penicillin Binding Proteins ◽  
Peptidoglycan Cell Wall ◽  
Class B ◽  
Shape Determination

ABSTRACT The peptidoglycan cell wall determines the shape and structural integrity of a bacterial cell. Class B penicillin-binding proteins (PBPs) carry a transpeptidase activity that cross-links peptidoglycan strands via their peptide side chains, and some of these proteins are directly involved in cell shape determination. No Bacillus subtilis PBP with a clear role in rod shape maintenance has been identified. However, previous studies showed that during outgrowth of pbpA mutant spores, the cells grew in an ovoid shape for several hours before they recovered and took on a normal rod shape. It was postulated that another PBP, expressed later during outgrowth, was able to compensate for the lack of the pbpA product, PBP2a, and to guide the formation of a rod shape. The B. subtilis pbpH (ykuA) gene product is predicted to be a class B PBP with greatest sequence similarity to PBP2a. We found that a pbpH-lacZ fusion was expressed at very low levels in early log phase and increased in late log phase. A pbpH null mutant was indistinguishable from the wild-type, but a pbpA pbpH double mutant was nonviable. When pbpH was placed under the control of an inducible promoter in a pbpA mutant, viability was dependent on pbpH expression. Growth of this strain in the absence of inducer resulted in conversion of the cells from rods to ovoid/round shapes and lysis. We conclude that PBP2a and PbpH play redundant roles in formation of a rod-shaped peptidoglycan cell wall.

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 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 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
Sign in / Sign up

Export Citation Format

Share Document