Wall Teichoic Acid Protects
            <i>Staphylococcus aureus</i>
            against Antimicrobial Fatty Acids from Human Skin

Kohler, Thomas P.; Weidenmaier, Christopher; Peschel, Andreas

doi:10.1128/jb.00221-09

Cited by 97 publications

(99 citation statements)

References 25 publications

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“…Microarray analysis revealed that the transcription of 245 genes is altered in a ⌬braS mutant (with the majority being downregulated). These 245 genes include several that are involved in transport, drug resistance, cell envelope synthesis, transcriptional regulation, amino acid metabolism, and virulence (126). Thus, BraRS has an important resistance role in S. aureus and functions to reprogram gene expression to modify cell envelope architecture, facilitating adaptation and survival.…”

Section: Bcers-like Two-component Systemsmentioning

confidence: 99%

Lantibiotic Resistance

Draper

Cotter

Hill

et al. 2015

Microbiol Mol Biol Rev

135

129

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SUMMARY The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry.

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Section: Bcers-like Two-component Systemsmentioning

confidence: 99%

Lantibiotic Resistance

Draper

Cotter

Hill

et al. 2015

Microbiol Mol Biol Rev

135

129

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“…Of note, WTAs are exposed at the S. aureus cell surface and they are required for PBP2a-mediated ␤-lactam antibiotic resistance Farha et al, 2013;Maki et al, 1994). Moreover, S. aureus mutants lacking WTA are susceptible to antimicrobial fatty acids from human skin (Kohler et al, 2009) and WTA contributes to S. aureus lysozyme resistance (Bera et al, 2007) suggesting a general protective role of WTA against antimicrobials. Because of its importance in vivo and in resistance to ␤-lactam antibiotics S. aureus WTA represents a very attractive target for the development of new antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus

Winstel

Xia

Peschel

2014

International Journal of Medical Microbiology

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a b s t r a c tThe thick peptidoglycan layers of Gram-positive bacteria are connected to polyanionic glycopolymers called wall teichoic acids (WTA). Pathogens such as Staphylococcus aureus, Listeria monocytogenes, or Enterococcus faecalis produce WTA with diverse, usually strain-specific structure. Extensive studies on S. aureus WTA mutants revealed important functions of WTA in cell division, growth, morphogenesis, resistance to antimicrobials, and interaction with host or phages. While most of the S. aureus WTA-biosynthetic genes have been identified it remained unclear for long how and why S. aureus glycosylates WTA with ␣-or ␤-linked N-acetylglucosamine (GlcNAc). Only recently the discovery of two WTA glycosyltransferases, TarM and TarS, yielded fundamental insights into the roles of S. aureus WTA glycosylation. Mutants lacking WTA GlcNAc are resistant towards most of the S. aureus phages and, surprisingly, TarS-mediated WTA ␤-O-GlcNAc modification is essential for ␤-lactam resistance in methicillin-resistant S. aureus. Notably, S. aureus WTA GlcNAc residues are major antigens and activate the complement system contributing to opsonophagocytosis. WTA glycosylation with a variety of sugars and corresponding glycosyltransferases were also identified in other Gram-positive bacteria, which paves the way for detailed investigations on the diverse roles of WTA modification with sugar residues.

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“…Deletion of LTA leads to temperature-sensitive strains only viable at temperatures lower than 30°C, and, interestingly, strains with deletions of both WTA and LTA are nonviable, suggesting some degree of redundancy in their respective roles (7). TAs have furthermore been implicated in resistance to antimicrobial molecules (8)(9)(10)(11), resistance to lysozyme (11), coping with environmental stresses (7,12), mediating interactions with receptors and biomaterials (6,13), induction of inflammation (14)(15)(16), phage binding (17,18), and biofilm formation (19). Faced with so many functions in an uncertain environment, TAs must remain highly adaptive, a large part of which is achieved by the D-alanylation and glycosylation of polyol hydroxyl groups.…”

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confidence: 99%

Structure and mechanism ofStaphylococcus aureusTarM, the wall teichoic acid α-glycosyltransferase

Sobhanifar

Worrall

Gruninger

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Unique to Gram-positive bacteria, wall teichoic acids are anionic glycopolymers cross-stitched to a thick layer of peptidoglycan. The polyol phosphate subunits of these glycopolymers are decorated with GlcNAc sugars that are involved in phage binding, genetic exchange, host antibody response, resistance, and virulence. The search for the enzymes responsible for GlcNAcylation in Staphylococcus aureus has recently identified TarM and TarS with respective α-and β-(1-4) glycosyltransferase activities. The stereochemistry of the GlcNAc attachment is important in balancing biological processes, such that the interplay of TarM and TarS is likely important for bacterial pathogenicity and survival. Here we present the crystal structure of TarM in an unusual ternary-like complex consisting of a polymeric acceptor substrate analog, UDP from a hydrolyzed donor, and an α-glyceryl-GlcNAc product formed in situ. These structures support an internal nucleophilic substitution-like mechanism, lend new mechanistic insight into the glycosylation of glycopolymers, and reveal a trimerization domain with a likely role in acceptor substrate scaffolding.glycosyltransferase | wall teichoic acid | cell wall | crystal structure | bacterial pathogenicity

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Wall Teichoic Acid Protects Staphylococcus aureus against Antimicrobial Fatty Acids from Human Skin

Cited by 97 publications

References 25 publications

Lantibiotic Resistance

Lantibiotic Resistance

Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus

Structure and mechanism ofStaphylococcus aureusTarM, the wall teichoic acid α-glycosyltransferase

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