scholarly journals Taking aim at wall teichoic acid synthesis: new biology and new leads for antibiotics

2013 ◽  
Vol 67 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Edward WC Sewell ◽  
Eric D Brown
Keyword(s):  
Teichoic Acid ◽  
Acid Synthesis ◽  
Wall Teichoic Acid ◽  
New Biology

scholarly journals Control of teichoic acid and teichuronic acid biosynthesis in chemostat cultures of Bacillus subtilis var. niger

1969 ◽  
Vol 111 (1) ◽  
pp. 1-5 ◽  
Author(s):  
D C Ellwood ◽  
D. W. Tempest
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Teichoic Acid ◽  
Extracellular Fluid ◽  
Acid Synthesis ◽  
Growth Cycle ◽  
Wall Material ◽  
Wall Teichoic Acid ◽  
Anionic Polymers ◽  
Teichuronic Acid

1. Quantitative determination of the anionic polymers present in the walls of Bacillus subtilis var. niger organisms undergoing transition, in a chemostat culture, from either Mg2+-limitation to PO43−-limitation or K+-limitation to PO43−-limitation showed that teichuronic acid synthesis started immediately the culture became PO43−-limited and proceeded at a rate substantially faster than the rate of biomass synthesis. 2. Simultaneously, the cell-wall teichoic acid content diminished at a rate greater than that due to dilution by newly synthesized wall material, and fragments of teichoic acid and mucopeptide accumulated in the culture extracellular fluid. 3. Equally rapid reverse changes occurred when a PO43−-limited B. subtilis var. niger culture was returned to being Mg2+-limited. 4. It is concluded that in this organism both teichoic acid and teichuronic acid syntheses are expressions of a single genotype, and a mechanism for the control of synthesis of both polymers is suggested. 5. These results are discussed with reference to the constantly changing environmental conditions that obtain in a batch culture and the variation in bacterial cell-wall composition that is reported to occur throughout the growth cycle.

scholarly journals Analysis of Bacillus subtilis tagAB andtagDEF Expression during Phosphate Starvation Identifies a Repressor Role for PhoP∼P

1998 ◽  
Vol 180 (3) ◽  
pp. 753-758 ◽  
Author(s):  
Wei Liu ◽  
Stephen Eder ◽  
F. Marion Hulett
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Teichoic Acid ◽  
Phosphate Starvation ◽  
Acid Synthesis ◽  
Pho Regulon ◽  
Wall Teichoic Acid ◽  
Negative Role ◽  
First Time ◽  
Starvation Conditions

ABSTRACT The tagAB and tagDEF operons, which are adjacent and divergently transcribed, encode genes responsible for cell wall teichoic acid synthesis in Bacillus subtilis. TheBacillus data presented here suggest that PhoP and PhoR are required for direct repression of transcription of the two operons under phosphate starvation conditions but have no regulatory role under phosphate-replete conditions. These data identify for the first time that PhoP∼P has a negative role in Pho regulon gene regulation.

scholarly journals LcpB Is a Pyrophosphatase Responsible for Wall Teichoic Acid Synthesis and Virulence in Staphylococcus aureus Clinical Isolate ST59

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Pan ◽  
Jing Guan ◽  
Yujie Li ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Molecular Mechanisms ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Cell Wall Synthesis ◽  
Wall Teichoic Acid ◽  
Independent Manner ◽  
Methicillin Resistant

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe pandemics primarily consisting of skin and soft tissue infections. However, the underlying pathomechanisms of the bacterium are yet to fully understood. The present study identifies LcpB protein, which belongs to the LytR-A-Psr (LCP) family, is crucial for cell wall synthesis and virulence in S. aureus. The findings revealed that LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis. The results also showed that LcpB regulates enzyme activity through specific key arginine sites in its LCP domain. Furthermore, knockout of lcpB in the CA-MRSA isolate ST59 resulted in enhanced hemolytic activity, enlarged of abscesses, and increased leukocyte infiltration. Meanwhile, we also found that LcpB regulates virulence in agr-independent manner and the key sites for pyrophosphatase of LcpB play critical roles in regulating the virulence. In addition, the results showed that the role of LcpB was different between methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). This study therefore highlights the dual role of LcpB in cell wall synthesis and regulation of virulence. These insights on the underlying molecular mechanisms can thus guide the development of novel anti-infective strategies.

scholarly journals Synthesis of CDP-Activated Ribitol for Teichoic Acid Precursors in Streptococcus pneumoniae

2008 ◽  
Vol 191 (4) ◽  
pp. 1200-1210 ◽  
Author(s):  
Stefanie Baur ◽  
Jon Marles-Wright ◽  
Stephan Buckenmaier ◽  
Richard J. Lewis ◽  
Waldemar Vollmer
Keyword(s):  
Streptococcus Pneumoniae ◽  
Cytoplasmic Membrane ◽  
Teichoic Acid ◽  
Lipoteichoic Acid ◽  
Acid Synthesis ◽  
Capsular Polysaccharides ◽  
Complex Cell ◽  
Wall Teichoic Acid ◽  
Key Enzyme

ABSTRACT Streptococcus pneumoniae has unusually complex cell wall teichoic acid and lipoteichoic acid, both of which contain a ribitol phosphate moiety. The lic region of the pneumococcal genome contains genes for the uptake and activation of choline, the attachment of phosphorylcholine to teichoic acid precursors, and the transport of these precursors across the cytoplasmic membrane. The role of two other, so far uncharacterized, genes, spr1148 and spr1149, in the lic region was determined. TarJ (spr1148) encodes an NADPH-dependent alcohol dehydrogenase for the synthesis of ribitol 5-phosphate from ribulose 5-phosphate. TarI (spr1149) encodes a cytidylyl transferase for the synthesis of cytidine 5′-diphosphate (CDP)-ribitol from ribitol 5-phosphate and cytidine 5′-triphosphate. We also present the crystal structure of TarI with and without bound CDP, and the structures present a rationale for the substrate specificity of this key enzyme. No transformants were obtained with insertion plasmids designed to interrupt the tarIJ genes, indicating that their function could be essential for cell growth. CDP-activated ribitol is a precursor for the synthesis of pneumococcal teichoic acids and some of the capsular polysaccharides. Thus, all eight genes in the lic region have a role in teichoic acid synthesis.

scholarly journals Wall Teichoic Acid Polymers Are Dispensable for Cell Viability in Bacillus subtilis

2006 ◽  
Vol 188 (23) ◽  
pp. 8313-8316 ◽  
Author(s):  
Michael A. D'Elia ◽  
Kathryn E. Millar ◽  
Terry J. Beveridge ◽  
Eric D. Brown
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Bacillus Subtilis ◽  
Cell Viability ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Extensive Literature ◽  
Wall Teichoic Acid ◽  
First Time ◽  
Similar Gene

ABSTRACT An extensive literature has established that the synthesis of wall teichoic acid in Bacillus subtilis is essential for cell viability. Paradoxically, we have recently shown that wall teichoic acid biogenesis is dispensable in Staphylococcus aureus (M. A. D'Elia, M. P. Pereira, Y. S. Chung, W. Zhao, A. Chau, T. J. Kenney, M. C. Sulavik, T. A. Black, and E. D. Brown, J. Bacteriol. 188:4183-4189, 2006). A complex pattern of teichoic acid gene dispensability was seen in S. aureus where the first gene (tarO) was dispensable and later acting genes showed an indispensable phenotype. Here we show, for the first time, that wall teichoic acid synthesis is also dispensable in B. subtilis and that a similar gene dispensability pattern is seen where later acting enzymes display an essential phenotype, while the gene tagO, whose product catalyzes the first step in the pathway, could be deleted to yield viable mutants devoid of teichoic acid in the cell wall.

scholarly journals The Amino Terminus of Bacillus subtilis TagB Possesses Separable Localization and Functional Properties

2007 ◽  
Vol 189 (19) ◽  
pp. 6816-6823 ◽  
Author(s):  
Amit P. Bhavsar ◽  
Michael A. D'Elia ◽  
Tiffany D. Sahakian ◽  
Eric D. Brown
Keyword(s):  
Bacillus Subtilis ◽  
Protein Function ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Amino Terminus ◽  
Membrane Localization ◽  
Membrane Targeting ◽  
Glycerol Phosphate ◽  
Wall Teichoic Acid ◽  
Necessary And Sufficient

ABSTRACT The function(s) of gram-positive wall teichoic acid is emerging with recent findings that it is an important virulence factor in the pathogen Staphylococcus aureus and that it is crucial to proper rod-shaped cell morphology of Bacillus subtilis. Despite its importance, our understanding of teichoic acid biosynthesis remains incomplete. The TagB protein has been implicated in the priming step of poly(glycerol phosphate) wall teichoic acid synthesis in B. subtilis. Work to date indicates that the TagB protein is localized to the membrane, where it adds a single glycerol phosphate residue to the nonreducing end of the undecaprenol-phosphate-linked N-acetylmannosamine-β(1,4)-N-acetylglucosamine-1-phosphate. Thus, membrane association is critical to TagB function. In this work we elucidate the mechanism of TagB membrane localization. We report the identification of a membrane targeting determinant at the amino terminus of TagB that is necessary and sufficient for membrane localization. The putative amphipathicity of this membrane targeting determinant was characterized and shown to be required for TagB function but not localization. This work shows for the first time that the amino terminus of TagB mediates membrane targeting and protein function.

scholarly journals The N-Acetylmannosamine Transferase Catalyzes the First Committed Step of Teichoic Acid Assembly in Bacillus subtilis and Staphylococcus aureus

2009 ◽  
Vol 191 (12) ◽  
pp. 4030-4034 ◽  
Author(s):  
Michael A. D'Elia ◽  
James A. Henderson ◽  
Terry J. Beveridge ◽  
David E. Heinrichs ◽  
Eric D. Brown
Keyword(s):  
Staphylococcus Aureus ◽  
Bacillus Subtilis ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Early Gene ◽  
Wall Teichoic Acid ◽  
And Staphylococcus Aureus ◽  
Made In

ABSTRACT There have been considerable strides made in the characterization of the dispensability of teichoic acid biosynthesis genes in recent years. A notable omission thus far has been an early gene in teichoic acid synthesis encoding the N-acetylmannosamine transferase (tagA in Bacillus subtilis; tarA in Staphylococcus aureus), which adds N-acetylmannosamine to complete the synthesis of undecaprenol pyrophosphate-linked disaccharide. Here, we show that the N-acetylmannosamine transferases are dispensable for growth in vitro, making this biosynthetic enzyme the last dispensable gene in the pathway, suggesting that tagA (or tarA) encodes the first committed step in wall teichoic acid synthesis.

scholarly journals Depletion of Undecaprenyl Pyrophosphate Phosphatases Disrupts Cell Envelope Biogenesis in Bacillus subtilis

2016 ◽  
Vol 198 (21) ◽  
pp. 2925-2935 ◽  
Author(s):  
Heng Zhao ◽  
Yingjie Sun ◽  
Jason M. Peters ◽  
Carol A. Gross ◽  
Ethan C. Garner ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Transcriptional Repression ◽  
Cell Envelope ◽  
Turgor Pressure ◽  
Teichoic Acid ◽  
Lethal Gene ◽  
Genetic Redundancy ◽  
Wall Teichoic Acid ◽  
Content Type ◽  
Lipid Ii

ABSTRACTThe integrity of the bacterial cell envelope is essential to sustain life by countering the high turgor pressure of the cell and providing a barrier against chemical insults. InBacillus subtilis, synthesis of both peptidoglycan and wall teichoic acids requires a common C55lipid carrier, undecaprenyl-pyrophosphate (UPP), to ferry precursors across the cytoplasmic membrane. The synthesis and recycling of UPP requires a phosphatase to generate the monophosphate form Und-P, which is the substrate for peptidoglycan and wall teichoic acid synthases. Using an optimizedclusteredregularlyinterspacedshortpalindromicrepeat (CRISPR) system with catalytically inactive (“dead”)CRISPR-associated protein9(dCas9)-based transcriptional repression system (CRISPR interference [CRISPRi]), we demonstrate thatB. subtilisrequires either of two UPP phosphatases, UppP or BcrC, for viability. We show that a third predicted lipid phosphatase (YodM), with homology to diacylglycerol pyrophosphatases, can also support growth when overexpressed. Depletion of UPP phosphatase activity leads to morphological defects consistent with a failure of cell envelope synthesis and strongly activates the σM-dependent cell envelope stress response, includingbcrC, which encodes one of the two UPP phosphatases. These results highlight the utility of an optimized CRISPRi system for the investigation of synthetic lethal gene pairs, clarify the nature of theB. subtilisUPP-Pase enzymes, and provide further evidence linking the σMregulon to cell envelope homeostasis pathways.IMPORTANCEThe emergence of antibiotic resistance among bacterial pathogens is of critical concern and motivates efforts to develop new therapeutics and increase the utility of those already in use. The lipid II cycle is one of the most frequently targeted processes for antibiotics and has been intensively studied. Despite these efforts, some steps have remained poorly defined, partly due to genetic redundancy. CRISPRi provides a powerful tool to investigate the functions of essential genes and sets of genes. Here, we used an optimized CRISPRi system to demonstrate functional redundancy of two UPP phosphatases that are required for the conversion of the initially synthesized UPP lipid carrier to Und-P, the substrate for the synthesis of the initial lipid-linked precursors in peptidoglycan and wall teichoic acid synthesis.

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