Effect of lipoteichoic acid on the uptake of Streptococcus pyogenes by HEp-2 cells

Sela, Sharon

doi:10.1016/s0378-1097(00)00444-4

Cited by 7 publications

(9 citation statements)

References 22 publications

(34 reference statements)

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“…LTA has been shown to play a role in GAS epithelial cell attachment and uptake (3,44). To assess the potential contribution of the D-alanyl modification of teichoic acids to these processes, we compared interactions of the WT and the ⌬dltA mutant with cultured monolayers of human pharyngeal epithelial cell line Hep-2.…”

Section: Resultsmentioning

confidence: 99%

“…LTA may be involved in processes such as the control of cell shape, autolytic enzyme activity, and maintenance of cation homeostasis (32). In GAS, LTA contributes to pharyngeal epithelial cell attachment (3,44). Classical biochemical and enzymologic studies indicated that GAS could incorporate D-alanine into its membrane-bound LTA through a two-step process involving a D-alanine-activating enzyme and D-alanine-D-alanyl carrier protein ligase (5).…”

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confidence: 99%

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d -Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion

Kristian

Datta

Weidenmaier³

et al. 2005

J Bacteriol

222

228

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Group A streptococcus (GAS) is a leading cause of severe, invasive human infections, including necrotizing fasciitis and toxic shock syndrome. An important element of the mammalian innate defense system against invasive bacterial infections such as GAS is the production of antimicrobial peptides (AMPs) such as cathelicidins. In this study, we identify a specific GAS phenotype that confers resistance to host AMPs. Allelic replacement of the dltA gene encoding D-alanine-D-alanyl carrier protein ligase in an invasive serotype M1 GAS isolate led to loss of teichoic acid D-alanylation and an increase in net negative charge on the bacterial surface. Compared to the wild-type (WT) parent strain, the GAS ⌬dltA mutant exhibited increased susceptibility to AMP and lysozyme killing and to acidic pH. While phagocytic uptake of WT and ⌬dltA mutants by human neutrophils was equivalent, neutrophil-mediated killing of the ⌬dltA strain was greatly accelerated. Furthermore, we observed the ⌬dltA mutant to be diminished in its ability to adhere to and invade cultured human pharyngeal epithelial cells, a likely proximal step in the pathogenesis of invasive infection. Thus, teichoic acid D-alanylation may contribute in multiple ways to the propensity of invasive GAS to bypass mucosal defenses and produce systemic infection.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

d -Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion

Kristian

Datta

Weidenmaier³

et al. 2005

J Bacteriol

222

228

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“…Growth of GAS in the presence of penicillin, which promotes the excretion of LTA, diminished their ability to adhere to epithelial cells (3). In studies of S. pyogenes internalization by epithelial cells (HEp-2), it was found that exogenous LTA inhibited entry of the bacterium into these cells (437). Entry is dependent on the initial LTA-mediated adhesion, and so the unique role of LTA in virulence would appear to be defined in GAS.…”

Section: Role In Virulencementioning

confidence: 99%

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

Neuhaus

Baddiley

2003

Microbiol Mol Biol Rev

896

1,097

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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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“…A recent report showed that free LTA specifically blocks intracellular invasion of Hep2 pharyngeal epithelial cells by S. pyogenes without affecting overall cellular adherence (44). In vivo, topical administration of LTA has also been shown to be effective in blocking vaginal colonization of pregnant mice by GBS (45).…”

Section: Figurementioning

confidence: 99%

Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid

Doran¹,

Engelson²,

Khosravi³

et al. 2005

J. Clin. Invest.

195

272

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Group B streptococci (GBSs) are the leading cause of neonatal meningitis. GBSs enter the CNS by penetrating the blood-brain barrier (BBB), which consists of specialized human brain microvascular endothelial cells (hBMECs). To identify GBS factors required for BBB penetration, we generated random mutant libraries of a virulent strain and screened for loss of hBMEC invasion in vitro. Two independent hypo-invasive mutants possessed disruptions in the same gene, invasion associated gene (iagA), which encodes a glycosyltransferase homolog. Allelic replacement of iagA in the GBS chromosome produced a 4-fold decrease in hBMEC invasiveness. Mice challenged with the GBS ∆iagA mutant developed bacteremia comparably to WT mice, yet mortality was significantly lower (20% vs. 90%), as was the incidence of meningitis. The glycolipid diglucosyldiacylglycerol, a cell membrane anchor for lipoteichoic acid (LTA) and predicted product of the IagA glycosyltransferase, was absent in the ∆iagA mutant, which consequently shed LTA into the media. Attenuation of virulence of the ∆iagA mutant was found to be independent of TLR2-mediated signaling, but bacterial supernatants from the ∆iagA mutant containing released LTA inhibited hBMEC invasion by WT GBS. Our data suggest that LTA expression on the GBS surface plays a role in bacterial interaction with BBB endothelium and the pathogenesis of neonatal meningitis.

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Effect of lipoteichoic acid on the uptake of Streptococcus pyogenes by HEp-2 cells

Cited by 7 publications

References 22 publications

d -Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion

d -Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion

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

Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid

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