scholarly journals Discovery of a Small Molecule that Blocks Wall Teichoic Acid Biosynthesis inStaphylococcus aureus

2009 ◽  
Vol 4 (10) ◽  
pp. 875-883 ◽  
Author(s):  
Jonathan G. Swoboda ◽  
Timothy C. Meredith ◽  
Jennifer Campbell ◽  
Stephanie Brown ◽  
Takashi Suzuki ◽  
...  
Keyword(s):  
Small Molecule ◽  
Teichoic Acid ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid

scholarly journals Hidden Mode of Action of Glycopeptide Antibiotics: Inhibition of Wall Teichoic Acid Biosynthesis

2017 ◽  
Vol 121 (16) ◽  
pp. 3925-3932 ◽  
Author(s):  
Manmilan Singh ◽  
James Chang ◽  
Lauryn Coffman ◽  
Sung Joon Kim
Keyword(s):  
Mode Of Action ◽  
Teichoic Acid ◽  
Glycopeptide Antibiotics ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid

In Vitro Reconstitution of Two Essential Steps in Wall Teichoic Acid Biosynthesis

2006 ◽  
Vol 1 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Cynthia Ginsberg ◽  
Yu-Hui Zhang ◽  
Yanqiu Yuan ◽  
Suzanne Walker
Keyword(s):  
Teichoic Acid ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid ◽  
In Vitro Reconstitution

TarO-specific inhibitors of wall teichoic acid biosynthesis restore β-lactam efficacy against methicillin-resistant staphylococci

2016 ◽  
Vol 8 (329) ◽  
pp. 329ra32-329ra32 ◽  
Author(s):  
Sang Ho Lee ◽  
Hao Wang ◽  
Marc Labroli ◽  
Sandra Koseoglu ◽  
Paul Zuck ◽  
...  
Keyword(s):  
Teichoic Acid ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid ◽  
Methicillin Resistant ◽  
Specific Inhibitors

scholarly journals Lesions in Teichoic Acid Biosynthesis in Staphylococcus aureus Lead to a Lethal Gain of Function in the Otherwise Dispensable Pathway

2006 ◽  
Vol 188 (12) ◽  
pp. 4183-4189 ◽  
Author(s):  
Michael A. D'Elia ◽  
Mark P. Pereira ◽  
Yu Seon Chung ◽  
Wenjun Zhao ◽  
Andrew Chau ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Essential Gene ◽  
Gene Knockout ◽  
Single Gene ◽  
Teichoic Acid ◽  
Extensive Study ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid ◽  
Gain Of Function ◽  
Essential Components

ABSTRACT An extensive study of teichoic acid biosynthesis in the model organism Bacillus subtilis has established teichoic acid polymers as essential components of the gram-positive cell wall. However, similar studies pertaining to therapeutically relevant organisms, such as Staphylococcus aureus, are scarce. In this study we have carried out a meticulous examination of the dispensability of teichoic acid biosynthetic enzymes in S. aureus. By use of an allelic replacement methodology, we examined all facets of teichoic acid assembly, including intracellular polymer production and export. Using this approach we confirmed that the first-acting enzyme (TarO) was dispensable for growth, in contrast to dispensability studies in B. subtilis. Upon further characterization, we demonstrated that later-acting gene products (TarB, TarD, TarF, TarIJ, and TarH) responsible for polymer formation and export were essential for viability. We resolved this paradox by demonstrating that all of the apparently indispensable genes became dispensable in a tarO null genetic background. This work suggests a lethal gain-of-function mechanism where lesions beyond the initial step in wall teichoic acid biosynthesis render S. aureus nonviable. This discovery poses questions regarding the conventional understanding of essential gene sets, garnered through single-gene knockout experiments in bacteria and higher organisms, and points to a novel drug development strategy targeting late steps in teichoic acid synthesis for the infectious pathogen S. aureus.

scholarly journals Late-Stage Polyribitol Phosphate Wall Teichoic Acid Biosynthesis in Staphylococcus aureus

2008 ◽  
Vol 190 (8) ◽  
pp. 3046-3056 ◽  
Author(s):  
Timothy C. Meredith ◽  
Jonathan G. Swoboda ◽  
Suzanne Walker
Keyword(s):  
Staphylococcus Aureus ◽  
Late Stage ◽  
Cell Envelope ◽  
Polyacrylamide Gel Electrophoresis ◽  
Teichoic Acid ◽  
Accessory Gene ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid ◽  
Accessory Gene Regulator ◽  
Acid Pathway

ABSTRACT Wall teichoic acids are cell wall polymers that maintain the integrity of the cellular envelope and contribute to the virulence of Staphylococcus aureus. Despite the central role of wall teichoic acid in S. aureus virulence, details concerning the biosynthetic pathway of the predominant wall teichoic acid polymer are lacking, and workers have relied on a presumed similarity to the putative polyribitol phosphate wall teichoic acid pathway in Bacillus subtilis. Using high-resolution polyacrylamide gel electrophoresis for analysis of wall teichoic acid extracted from gene deletion mutants, a revised assembly pathway for the late-stage ribitol phosphate-utilizing enzymes is proposed. Complementation studies show that a putative ribitol phosphate polymerase, TarL, catalyzes both the addition of the priming ribitol phosphate onto the linkage unit and the subsequent polymerization of the polyribitol chain. It is known that the putative ribitol primase, TarK, is also a bifunctional enzyme that catalyzes both ribitol phosphate priming and polymerization. TarK directs the synthesis of a second, electrophoretically distinct polyribitol-containing teichoic acid that we designate K-WTA. The biosynthesis of K-WTA in S. aureus strain NCTC8325 is repressed by the accessory gene regulator (agr) system. The demonstration of regulated wall teichoic acid biosynthesis has implications for cell envelope remodeling in relation to S. aureus adhesion and pathogenesis.

scholarly journals Development and Characterization of a Xylose-Dependent System for Expression of Cloned Genes inBacillus subtilis: Conditional Complementation of a Teichoic Acid Mutant

2001 ◽  
Vol 67 (1) ◽  
pp. 403-410 ◽  
Author(s):  
Amit P. Bhavsar ◽  
Xumei Zhao ◽  
Eric D. Brown
Keyword(s):  
Expression System ◽  
Teichoic Acid ◽  
Temperature Sensitive ◽  
Xylose Utilization ◽  
Acid Biosynthesis ◽  
Wall Teichoic Acid ◽  
System Versus ◽  
Essential Function ◽  
Responsive Element

ABSTRACT We have developed a xylose-dependent expression system for tight and modulated expression of cloned genes in Bacillus subtilis. The expression system is contained on plasmid pSWEET for integration at the amyE locus of B. subtilis and incorporates components of the well-characterized, divergently transcribed xylose utilization operon. The system contains the xylose repressor encoded by xylR, the promoter and 5′ portion of xylA containing an optimized catabolite-responsive element, and intergenic xyl operator sequences. We have rigorously compared this expression system to the isopropyl-β-d-thiogalactopyranoside-inducedspac system using a thermostable β-galactosidase reporter (BgaB) and found the xyl promoter-operator to have a greater capacity for modulated expression, a higher induction/repression ratio (279-fold for the xyl system versus 24-fold with the spac promoter), and lower levels of expression in the absence of an inducer. We have used this system to probe an essential function in wall teichoic acid biosynthesis inB. subtilis. Expression of the teichoic acid biosynthesis gene tagD, encoding glycerol-3-phosphate cytidylyltransferase, from the xylose-based expression system integrated at amyE exhibited xylose-dependent complementation of the temperature-sensitive mutant tag-12when grown at the nonpermissive temperature. Plasmid pSWEET thus provides a robust new expression system for conditional complementation in B. subtilis.

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