A Continuum of Anionic Charge: Structures and Functions of d-Alanyl-Teichoic Acids in Gram-Positive Bacteria

SUMMARY Teichoic acids (TAs) are major wall and membrane components of most gram-positive bacteria. With few exceptions, they are polymers of glycerol-phosphate or ribitol-phosphate to which are attached glycosyl and d-alanyl ester residues. Wall TA is attached to peptidoglycan via a linkage unit, whereas lipoteichoic acid is attached to glycolipid intercalated in the membrane. Together with peptidoglycan, these polymers make up a polyanionic matrix that functions in (i) cation homeostasis; (ii) trafficking of ions, nutrients, proteins, and antibiotics; (iii) regulation of autolysins; and (iv) presentation of envelope proteins. The esterification of TAs with d-alanyl esters provides a means of modulating the net anionic charge, determining the cationic binding capacity, and displaying cations in the wall. This review addresses the structures and functions of d-alanyl-TAs, the d-alanylation system encoded by the dlt operon, and the roles of TAs in cell growth. The importance of dlt in the physiology of many organisms is illustrated by the variety of mutant phenotypes. In addition, advances in our understanding of d-alanyl ester function in virulence and host-mediated responses have been made possible through targeted mutagenesis of dlt. Studies of the mechanism of d-alanylation have identified two potential targets of antibacterial action and provided possible screening reactions for designing novel agents targeted to d-alanyl-TA synthesis.

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How Teichoic Acids Could Support a Periplasm in Gram-Positive Bacteria, and Let Cell Division Cheat Turgor Pressure

Frontiers in Microbiology ◽

10.3389/fmicb.2021.664704 ◽

2021 ◽

Vol 12 ◽

Author(s):

Harold P. Erickson

Keyword(s):

Cell Division ◽

Charge Density ◽

Turgor Pressure ◽

Support Pressure ◽

Periplasmic Space ◽

Gram Positive ◽

Teichoic Acids ◽

Gram Positive Bacteria ◽

Peptidoglycan Cell Wall ◽

Anionic Charge

The cytoplasm of bacteria is maintained at a higher osmolality than the growth medium, which generates a turgor pressure. The cell membrane (CM) cannot support a large turgor, so there are two possibilities for transferring the pressure to the peptidoglycan cell wall (PGW): (1) the CM could be pressed directly against the PGW, or (2) the CM could be separated from the PGW by a periplasmic space that is isoosmotic with the cytoplasm. There is strong evidence for gram-negative bacteria that a periplasm exists and is isoosmotic with the cytoplasm. No comparable studies have been done for gram-positive bacteria. Here I suggest that a periplasmic space is probably essential in order for the periplasmic proteins to function, including especially the PBPs that remodel the peptidoglycan wall. I then present a semi-quantitative analysis of how teichoic acids could support a periplasm that is isoosmotic with the cytoplasm. The fixed anionic charge density of teichoic acids in the periplasm is ∼0.5 M, which would bring in ∼0.5 M Na+ neutralizing ions. This approximately balances the excess osmolality of the cytoplasm that would produce a turgor pressure of 19 atm. The 0.5 M fixed charge density is similar to that of proteoglycans in articular cartilage, suggesting a comparability ability to support pressure. An isoosmotic periplasm would be especially important for cell division, since it would allow CM constriction and PGW synthesis to avoid turgor pressure.

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Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

Scientific Reports ◽

10.1038/s41598-021-92744-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsukasa Tominari ◽

Ayumi Sanada ◽

Ryota Ichimaru ◽

Chiho Matsumoto ◽

Michiko Hirata ◽

...

Keyword(s):

Cell Wall ◽

Bone Loss ◽

Alveolar Bone ◽

Osteoclast Differentiation ◽

Lipoteichoic Acid ◽

Alveolar Bone Loss ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

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Mixed liposomes containing gram-positive bacteria lipids: Lipoteichoic acid (LTA) induced structural changes

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2020.111551 ◽

2021 ◽

Vol 199 ◽

pp. 111551

Author(s):

Bhavesh Bharatiya ◽

Gang Wang ◽

Sarah E. Rogers ◽

Jan Skov Pedersen ◽

Stephen Mann ◽

...

Keyword(s):

Structural Changes ◽

Lipoteichoic Acid ◽

Gram Positive ◽

Gram Positive Bacteria

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Teichoic Acids, Lipoteichoic Acids and Other Secondary Cell Wall and Membrane Polysaccharides of Gram-Positive Bacteria

Molecular Medical Microbiology ◽

10.1016/b978-0-12-397169-2.00005-6 ◽

2015 ◽

pp. 91-103 ◽

Cited By ~ 1

Author(s):

Ian R. Poxton

Keyword(s):

Cell Wall ◽

Secondary Cell Wall ◽

Gram Positive ◽

Teichoic Acids ◽

Gram Positive Bacteria ◽

Lipoteichoic Acids

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Wall Teichoic Acids of Gram-Positive Bacteria

Annual Review of Microbiology ◽

10.1146/annurev-micro-092412-155620 ◽

2013 ◽

Vol 67 (1) ◽

pp. 313-336 ◽

Cited By ~ 377

Author(s):

Stephanie Brown ◽

John P. Santa Maria ◽

Suzanne Walker

Keyword(s):

Gram Positive ◽

Teichoic Acids ◽

Gram Positive Bacteria ◽

Wall Teichoic Acids

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L-Ficolin Specifically Binds to Lipoteichoic Acid, a Cell Wall Constituent of Gram-Positive Bacteria, and Activates the Lectin Pathway of Complement

The Journal of Immunology ◽

10.4049/jimmunol.172.2.1198 ◽

2004 ◽

Vol 172 (2) ◽

pp. 1198-1202 ◽

Cited By ~ 186

Author(s):

Nicholas J. Lynch ◽

Silke Roscher ◽

Thomas Hartung ◽

Siegfried Morath ◽

Misao Matsushita ◽

...

Keyword(s):

Cell Wall ◽

Lipoteichoic Acid ◽

Lectin Pathway ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Cell Wall Constituent ◽

A Cell

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Mechanism of Gram-positive Shock: Identification of Peptidoglycan and Lipoteichoic Acid Moieties Essential in the Induction of Nitric Oxide Synthase, Shock, and Multiple Organ Failure

Journal of Experimental Medicine ◽

10.1084/jem.188.2.305 ◽

1998 ◽

Vol 188 (2) ◽

pp. 305-315 ◽

Cited By ~ 164

Author(s):

Ken M. Kengatharan ◽

Sjef De Kimpe ◽

Caroline Robson ◽

Simon J. Foster ◽

Christoph Thiemermann

Keyword(s):

Nitric Oxide ◽

Multiple Organ Failure ◽

Organ Failure ◽

Lipoteichoic Acid ◽

Interferon Γ ◽

Multiple Organ ◽

Organ Injury ◽

Gram Positive ◽

Gram Positive Bacteria ◽

No Formation

The incidence of septic shock caused by gram-positive bacteria has risen markedly in the last few years. It is largely unclear how gram-positive bacteria (which do not contain endotoxin) cause shock and multiple organ failure. We have discovered recently that two cell wall fragments of the pathogenic gram-positive bacterium Staphylococcus aureus, lipoteichoic acid (LTA) and peptidoglycan (PepG), synergize to cause the induction of nitric oxide (NO) formation, shock, and organ injury in the rat. We report here that a specific fragment of PepG, N-acetylglucosamine-β-[1→ 4]-N-acetylmuramyl-l-alanine–d-isoglutamine, is the moiety within the PepG polymer responsible for the synergism with LTA (or the cytokine interferon γ) to induce NO formation in the murine macrophage cell line J774.2. However, this moiety is also present in the PepG of the nonpathogenic bacterium Bacillus subtilis. We have discovered subsequently that S. aureus LTA synergizes with PepG from either bacterium to cause enhanced NO formation, shock, and organ injury in the rat, whereas the LTA from B. subtilis does not synergize with PepG of either bacterium. Thus, we propose that the structure of LTA determines the ability of a particular bacterium to cause shock and multiple organ failure (pathogenicity), while PepG acts to amplify any response induced by LTA.

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