β-sitosterol interacts with pneumolysin to prevent Streptococcus pneumoniae infection

Li, Hongen; Zhao, Xiaoru; Wang, Jianfeng; Yu, Dong; Meng, Shaoping; Li, Rui; Niu, Xiaodi; Deng, Xuming

doi:10.1038/srep17668

Cited by 55 publications

(56 citation statements)

References 31 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of a recent study indicate that rumen microorganisms may degrade several cyanotoxins [33], the threat from cyanotoxins cannot be ignored. Our results revealed that BSS might inhibit the growth of cyanobacteria, since its antibacterial activity has been documented [34,35].…”

Section: Discussionmentioning

confidence: 53%

β-Sitosterol Attenuates High Grain Diet-Induced Inflammatory Stress and Modifies Rumen Fermentation and Microbiota in Sheep

Xia

Sun

Fan

et al. 2020

Animals

View full text Add to dashboard Cite

β-sitosterol (BSS) is a plant-derived natural bioactive compound, its cellular mechanism of anti-inflammatory activity has been proven recently. Little information is available regarding the application of BSS on ruminants under high grain diet. The objective of this study was to evaluate the effects of dietary BSS supplementation on inflammatory response, ruminal fermentation characteristics and the composition of the ruminal bacterial community under high grain diet. Eight rumen-cannulated Hu sheep (59.7 ± 4.8 kg of initial body weight) were randomly assigned into a replicated 4 × 4 Latin square design trial. Sheep were fed a high grain diet (non-fiber carbohydrate: neutral detergent fiber = 2.03) supplemented either with 0.25 (LBS), 0.5 (MBS), 1.0 (HBS) or without (CON) g BSS /kg dry matter diet. On day 21 of each period, rumen content samples were obtained at 6 h postfeeding, and blood samples were obtained before morning feeding. The data showed that compared with control group, Dietary BSS supplementation decreased serum concentrations of tumor necrosis factor, interleukin (IL)-6, and IL-1β. The ruminal pH and acetate concentration for BSS treatment were improved, while concentration of propionate, butyrate and lactate was decreased. The result of Illumina MiSeq sequencing of 16S rRNA gene revealed that BSS addition can increase the proportion of Prevotella_1, Rikenellaceae_RC9_gut_group, Prevotella_7, and Selenomonas_1, and decrease the proportion of Lachnospiraceae_NK3A20_group. These results indicated that BSS attenuates high grain diet-induced inflammatory response and modifies ruminal fermentation. In addition, the BSS dietary supplementation at the level of 0.5 g/kg is recommended in sheep.

show abstract

Section: Discussionmentioning

confidence: 53%

β-Sitosterol Attenuates High Grain Diet-Induced Inflammatory Stress and Modifies Rumen Fermentation and Microbiota in Sheep

Xia

Sun

Fan

et al. 2020

Animals

View full text Add to dashboard Cite

show abstract

“…EGCG can bind to the cleft between domains three and four in PLY via hydrogen bonding and hydrophobic interactions. This cleft is reported to participate in reactivity and is important for PLY . In detail, the binding model of EGCG with PLY revealed that the side chain of EGCG can form strong interactions with Ser256, Glu277, Tyr358 and Arg359, respectively.…”

Section: Resultsmentioning

confidence: 99%

Epigallocatechin gallate inhibits Streptococcus pneumoniae virulence by simultaneously targeting pneumolysin and sortase A

Meng

Teng

et al. 2017

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Streptococcus pneumoniae (pneumococcus), the causative agent of several human diseases, possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. Pneumolysin (PLY), an important virulence factor, is a member of the cholesterol‐dependent cytolysin family and has cytolytic activity. Sortase A (SrtA), another crucial pneumococcal virulence determinate, contributes greatly to the anchoring of many virulence‐associated surface proteins to the cell wall. In this study, epigallocatechin gallate (EGCG), a natural compound with little known antipneumococcal activity, was shown to directly inhibit PLY‐mediated haemolysis and cytolysis by blocking the oligomerization of PLY and simultaneously reduce the peptidase activity of SrtA. The biofilm formation, production of neuraminidase A (NanA, the pneumococcal surface protein anchored by SrtA), and bacterial adhesion to human epithelial cells (Hep2) were inhibited effectively when S. pneumoniae D39 was cocultured with EGCG. The results from molecular dynamics simulations and mutational analysis confirmed the interaction of EGCG with PLY and SrtA, and EGCG binds to Glu277, Tyr358, and Arg359 in PLY and Thr169, Lys171, and Phe239 in SrtA. In vivo studies further demonstrated that EGCG protected mice against S. pneumoniae pneumonia. Our results imply that EGCG is an effective inhibitor of both PLY and SrtA and that an antivirulence strategy that directly targets PLY and SrtA using EGCG is a promising therapeutic option for S. pneumoniae pneumonia.

show abstract

“…103 Also included in this category are βsitosterol, a plant-derived cholesterol mimic, as well as liposomes composed of sphingomyelin/cholesterol. [104][105][106] Several other plant-derived agents, viz.…”

Section: Inhibitors Of the Cytolytic Activity Of Pneumolysinmentioning

confidence: 99%

Pneumolysin as a potential therapeutic target in severe pneumococcal disease

Feldman

2017

Journal of Infection

View full text Add to dashboard Cite

Acute pulmonary and cardiac injury remain significant causes of morbidity and mortality in those afflicted with severe pneumococcal disease, with the risk for early mortality often persisting several years beyond clinical recovery. Although remaining to be firmly established in the clinical setting, a considerable body of evidence, mostly derived from murine models of experimental infection, has implicated the pneumococcal, cholesterol-binding, pore-forming toxin, pneumolysin (Ply), in the pathogenesis of lung and myocardial dysfunction. Topics covered in this review include the burden of pneumococcal disease, risk factors, virulence determinants of the pneumococcus, complications of severe disease, antibiotic and adjuvant therapies, as well as the structure of Ply and the role of the toxin in disease pathogenesis. Given the increasing recognition of the clinical potential of Ply-neutralisation strategies, the remaining sections of the review are focused on updates of the types, benefits and limitations of currently available therapies which may attenuate, directly and/or indirectly, the injurious actions of Ply. These include recently described experimental therapies such as various phytochemicals and lipids, and a second group of more conventional agents the members of which remain the subject of ongoing clinical evaluation. This latter group, which is covered more extensively, encompasses macrolides, statins, corticosteroids, and platelet-targeted therapies, particularly aspirin.

show abstract

β-sitosterol interacts with pneumolysin to prevent Streptococcus pneumoniae infection

Cited by 55 publications

References 31 publications

β-Sitosterol Attenuates High Grain Diet-Induced Inflammatory Stress and Modifies Rumen Fermentation and Microbiota in Sheep

β-Sitosterol Attenuates High Grain Diet-Induced Inflammatory Stress and Modifies Rumen Fermentation and Microbiota in Sheep

Epigallocatechin gallate inhibits Streptococcus pneumoniae virulence by simultaneously targeting pneumolysin and sortase A

Pneumolysin as a potential therapeutic target in severe pneumococcal disease

Contact Info

Product

Resources

About