scholarly journals Genomic characterization of ribitol teichoic acid synthesis in Staphylococcus aureus: genes, genomic organization and gene duplication

BMC Genomics ◽  
2006 ◽  
Vol 7 (1) ◽  
Author(s):  
Ziliang Qian ◽  
Yanbin Yin ◽  
Yong Zhang ◽  
Lingyi Lu ◽  
Yixue Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gene Duplication ◽  
Genomic Organization ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Genomic Characterization

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 A Staphylococcus aureus clpX Mutant Used as a Unique Screening Tool to Identify Cell Wall Synthesis Inhibitors that Reverse β-Lactam Resistance in MRSA

2021 ◽  
Vol 8 ◽  
Author(s):  
Kristoffer T. Bæk ◽  
Camilla Jensen ◽  
Maya A. Farha ◽  
Tobias K. Nielsen ◽  
Ervin Paknejadi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
High Throughput Screening ◽  
Bacterial Infections ◽  
Screening Tool ◽  
Acquired Resistance ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Biologically Active ◽  
Cell Wall Synthesis

Staphylococcus aureus is a leading cause of bacterial infections world-wide. Staphylococcal infections are preferentially treated with β-lactam antibiotics, however, methicillin-resistant S. aureus (MRSA) strains have acquired resistance to this superior class of antibiotics. We have developed a growth-based, high-throughput screening approach that directly identifies cell wall synthesis inhibitors capable of reversing β-lactam resistance in MRSA. The screen is based on the finding that S. aureus mutants lacking the ClpX chaperone grow very poorly at 30°C unless specific steps in teichoic acid synthesis or penicillin binding protein (PBP) activity are inhibited. This property allowed us to exploit the S. aureus clpX mutant as a unique screening tool to rapidly identify biologically active compounds that target cell wall synthesis. We tested a library of ∼50,000 small chemical compounds and searched for compounds that inhibited growth of the wild type while stimulating growth of the clpX mutant. Fifty-eight compounds met these screening criteria, and preliminary tests of 10 compounds identified seven compounds that reverse β-lactam resistance of MRSA as expected for inhibitors of teichoic acid synthesis. The hit compounds are therefore promising candidates for further development as novel combination agents to restore β-lactam efficacy against MRSA.

Synthesis of Microcapsule by Staphylococcus aureus Is Not Responsive to Environmental Phosphate Concentrations

1998 ◽  
Vol 66 (8) ◽  
pp. 4004-4007 ◽  
Author(s):  
Karen F. Fox ◽  
George C. Stewart ◽  
Alvin Fox
Keyword(s):  
Mass Spectrometry ◽  
Staphylococcus Aureus ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Growth Conditions ◽  
Phosphate Concentration ◽  
Gas Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry ◽  
Teichuronic Acid ◽  
Environmental Component

ABSTRACT The polysaccharide microcapsule of Staphylococcus aureus has been reported to be differentially expressed depending on growth conditions, with phosphate concentration being the critical environmental component. This study evaluated the effect of growth of a serotype 8 strain of S. aureus in phosphate-replete and phosphate-limiting media on microcapsule production. The presence of the cell wall polymers microcapsule and teichoic acid was measured by both gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Production of microcapsule was unaffected by changes in the environmental phosphate concentration. There was, additionally, no evidence for a shift from teichoic acid to teichuronic acid synthesis.

scholarly journals Bacterial Targets of Antibiotics in Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 398
Author(s):  
Harshad Lade ◽  
Jae-Seok Kim
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Accessory Gene ◽  
Methicillin Resistant ◽  
Accessory Gene Regulator ◽  
Healthcare Settings ◽  
Lipid Ii ◽  
Novel Therapeutic Strategies

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent bacterial pathogens and continues to be a leading cause of morbidity and mortality worldwide. MRSA is a commensal bacterium in humans and is transmitted in both community and healthcare settings. Successful treatment remains a challenge, and a search for new targets of antibiotics is required to ensure that MRSA infections can be effectively treated in the future. Most antibiotics in clinical use selectively target one or more biochemical processes essential for S. aureus viability, e.g., cell wall synthesis, protein synthesis (translation), DNA replication, RNA synthesis (transcription), or metabolic processes, such as folic acid synthesis. In this review, we briefly describe the mechanism of action of antibiotics from different classes and discuss insights into the well-established primary targets in S. aureus. Further, several components of bacterial cellular processes, such as teichoic acid, aminoacyl-tRNA synthetases, the lipid II cycle, auxiliary factors of β-lactam resistance, two-component systems, and the accessory gene regulator quorum sensing system, are discussed as promising targets for novel antibiotics. A greater molecular understanding of the bacterial targets of antibiotics has the potential to reveal novel therapeutic strategies or identify agents against antibiotic-resistant pathogens.

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 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.

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