Exposing a chink in the armor of methicillin-resistant
            <i>Staphylococcus aureus</i>

Sutcliffe, Iain C.

doi:10.1073/pnas.1216817109

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…Along this line there is evidence that PBP2a and PBP4 interact with WTA (Atilano et al, 2010;Qamar and Golemi-Kotra, 2012). However, it is also possible that WTA glycosylation affects the physicochemical properties of the peptidoglycan matrix by influencing the cell wall milieu (Sutcliffe, 2012).…”

Section: Functional Roles Of Wta Glycosylation In S Aureusmentioning

confidence: 90%

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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Section: Functional Roles Of Wta Glycosylation In S Aureusmentioning

confidence: 90%

Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus

Winstel

Xia

Peschel

2014

International Journal of Medical Microbiology

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“…Proper tailoring of the teichoic acids is critical to MRSA virulence. 45,303,333,346,358,740 Interference with D-Ala tailoring of the teichoic acids of both Enterococci and S. aureus strains sensitizes these bacteria to β-lactams. 361,741 Interference with D-Ala (and glycosylation) 400 tailoring of the teichoic acids represents opportunity for antibacterial discovery.…”

Section: β-Lactams Against Bacterial Fortressesmentioning

confidence: 99%

“…Variations among the teichoic acid structures are reviewed . Given the emergence of the teichoic acids as essential to an understanding of antibiotic resistance, their role (no longer “secondary”) as polymers of the cell wall has been reviewed from different vantages. ,,,,− These reviews show a transition in the understanding of the teichoic acids from incidental structural entities of the cell envelope, to recognition that each (the WTA and the LTA) confers critical and essential character. The LTAs of the cell envelope are long recognized as structurally essential under almost all circumstances, whereas the WTAs are not .…”

Section: Gram-positive Cell Envelopementioning

confidence: 99%

“…The altered electrostatic character of WTA as a result of d -Ala decoration may represent the basis for Atl localization. ,, A conceptual proposal for WTA·Atl complexation is given in Figure . Proper tailoring of the teichoic acids is critical to MRSA virulence. ,,,,, Interference with d -Ala tailoring of the teichoic acids of both Enterococci and S. aureus strains sensitizes these bacteria to β-lactams. , Interference with d -Ala (and glycosylation) tailoring of the teichoic acids represents opportunity for antibacterial discovery. , …”

Section: Against the Fortressmentioning

confidence: 99%

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β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium

Fisher

Mobashery

2020

Chem. Rev.

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The biological diversity of the unicellular bacteriawhether assessed by shape, food, metabolism, or ecological nichesurely rivals (if not exceeds) that of the multicellular eukaryotes. The relationship between bacteria whose ecological niche is the eukaryote, and the eukaryote, is often symbiosis or stasis. Some bacteria, however, seek advantage in this relationship. One of the most successfulto the disadvantage of the eukaryoteis the small (less than 1 μm diameter) and nearly spherical Staphylococcus aureus bacterium. For decades, successful clinical control of its infection has been accomplished using β-lactam antibiotics such as the penicillins and the cephalosporins. Over these same decades S. aureus has perfected resistance mechanisms against these antibiotics, which are then countered by new generations of β-lactam structure. This review addresses the current breadth of biochemical and microbiological efforts to preserve the future of the β-lactam antibiotics through a better understanding of how S. aureus protects the enzyme targets of the β-lactams, the penicillin-binding proteins. The penicillin-binding proteins are essential enzyme catalysts for the biosynthesis of the cell wall, and understanding how this cell wall is integrated into the protective cell envelope of the bacterium may identify new antibacterials and new adjuvants that preserve the efficacy of the β-lactams.

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Introduction

2016

Indole Ring Synthesis

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Exposing a chink in the armor of methicillin-resistant Staphylococcus aureus

Cited by 5 publications

References 16 publications

Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus

Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus

β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium

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