Pneumolysin Mediates Platelet Activation In Vitro

Nel, Jan Gert; Durandt, Chrisna; Mitchell, Tim; Feldman, Charles; Tintinger, Gregory Ronald

doi:10.1007/s00408-016-9900-5

Cited by 35 publications

(39 citation statements)

References 24 publications

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“…So far, only the secreted pore-forming toxin pneumolysin could be identified as a platelet activation agent, which is in contrast to the observations made by Keane et al [90]. Pneumolysin (Ply) activated human platelets in vitro via induction of intracellular calcium fluxes and P-selectin expression at concentrations similar to those found in severe pneumococcal infections [94]. However, platelet activation was dependent on pore-formation and did not involve an agonist-receptor mediated outside-to-inside signaling cascade.…”

Section: Pneumococcal and Staphylococcal Interactions With Soluble Plcontrasting

confidence: 50%

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

Binsker¹,

Kohler²,

Hammerschmidt³

2019

J Innate Immun

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A successful colonization of different compartments of the human host requires multifactorial contacts between bacterial surface proteins and host factors. Extracellular matrix proteins and matricellular proteins such as thrombospondin-1 play a pivotal role as adhesive substrates to ensure a strong interaction with pathobionts like the Gram-positive Streptococcus pneumoniae and Staphylococcus aureus. The human glycoprotein thrombospondin-1 is a component of the extracellular matrix and is highly abundant in the bloodstream during bacteremia. Human platelets secrete thrombospondin-1, which is then acquired by invading pathogens to facilitate colonization and immune evasion. Gram-positive bacteria express a broad spectrum of surface-exposed proteins, some of which also recognize thrombospondin-1. This review highlights the importance of thrombospondin-1 as an adhesion substrate to facilitate colonization, and we summarize the variety of thrombospondin-1-binding proteins of S. pneumoniae and S. aureus.

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Section: Pneumococcal and Staphylococcal Interactions With Soluble Plcontrasting

confidence: 50%

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

Binsker¹,

Kohler²,

Hammerschmidt³

2019

J Innate Immun

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“…Authors concluded that the upregulation of the sP‐selectin is secondary to increased levels of bacterial products such as LPS and the pro‐inflammatory stimuli of sNOX2‐dp. Finally, pneumolysin (Ply), a pore‐forming toxin produced by S. pneumoniae , has been recently shown to have the capacity to induce platelet activation, as determined by higher levels of sP‐selectin in tissue culture experiments …”

Section: Mechanisms Of Cardiac Damage During Capmentioning

confidence: 99%

Pneumonia as a cardiovascular disease

Restrepo

Reyes

2018

Respirology

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Community-acquired pneumonia (CAP) is an important cause of death around the globe. Up to 30% of patients admitted to hospital for CAP develop cardiovascular complications (i.e. new/worsening heart failure, new/-worsening arrhythmias, myocardial infarctions and/or strokes), acutely and up to 10 years thereafter. Cardiac complications result from complex interactions between preexisting conditions, relative ischaemia, upregulation of the sympathetic system, systemic inflammation and direct pathogen-mediated damage to the cardiovascular system. The exact mechanisms underlying the direct host-pathogen interactions are of great interest to identify potential therapeutic and preventative targets for CAP. In this review, we summarize the epidemiological data, risk factors and the pathogendriven cardiovascular damage affecting patients with CAP.Key words: arrhythmias, heart failure, myocardial infarction, pneumonia.Abbreviations: ACE, angiotensin-converting enzyme; ACS, acute coronary syndrome; ARB, angiotensin receptor blocker; CAP, community-acquired pneumonia; CC, cardiovascular complication; CRP, C-reactive protein; CVD, cardiovascular disease; IPD, invasive pneumococcal disease; MI, myocardial infarction; NHP, non-human primates; PAR, protease-activated receptor; Ply, pneumolysin; RR, risk ratio; sP-selectin, soluble Pselectin; SRMA, systematic review and meta-analysis.Glossary: ST segment, The ST segment is the flat, isoelectric section of the electrocardiogram (ECG) between the end of the S wave (the J point) and the beginning of the T wave

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“…PLY, one of the most extensively studied CDCs, exhibits several biological properties, such as activation of the complement system [20], platelets [21], and NLR family pyrin domain containing protein 3 (NLRP3) inflammasome [22] or stimulation of pattern recognition receptors (PRRs) [23,24]. Studies indicated that the pore-forming activity and pathogen-associated molecular pattern (PAMP) activity of the toxin form the foundation for most of the previously mentioned biological properties.…”

Section: Introductionmentioning

confidence: 99%

Replacing the 238th aspartic acid with an arginine impaired the oligomerization activity and inflammation-inducing property of pyolysin

Zhang

Wang

et al. 2018

Virulence

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Trueperella pyogenes (T. pyogenes) is an important opportunistic pathogen. Pyolysin (PLO) importantly contributes to the pathogenicity of T. pyogenes. However, the relationship between the structure and function and the virulence of PLO is not well documented. In the current study, recombinant PLO (rPLO) and three rPLO mutants were prepared. rPLO D238R, a mutant with the 238th aspartic acid replaced with an arginine, showed impairment in oligomerization activity on cholesterol-containing liposome and pore-forming activity on sheep red blood cell membrane. Further study employing the prepared mutants confirmed that the pore-forming activity of PLO is essential for inducing excessive inflammation responses in mice by upregulating the expression levels of IL-1β, TNF-α, and IL-6. By contrast, rPLO P499F, another mutant with impaired cell membrane binding capacity, elicited an inflammation response that was dependent on pathogen-associated molecular pattern (PAMP) activity, given that the mutant significantly upregulated the expression of IL-10 in macrophages and in mice, whereas rPLO did not. Results indicated that domain 1 of the PLO molecule plays an important role in maintaining pore-forming activity. Moreover, the PLO pore-forming activity and not PAMP activity is responsible for the inflammation-inducing effect of PLO. The results of this study provided new information for research field on the structure, function, and virulence of PLO.Abbreviations: T. pyogenes: Trueperella pyogenes; PLO: Pyolysin; rPLO: recombinant PLO; PAMP: pathogen-associated molecular pattern; CDCs: cholesterol-dependent cytolysins; PLY: pneumolysin; NLRP3: NLR family pyrin domain containing protein 3; PRRs: pattern recognition receptors; Asp: aspartic acid; TLR4: Toll-like receptor 4; Arg: arginine; Asn: asparagine; IPTG: Isopropyl-β-d-thiogalactoside; PBS: phosphate-buffered saline; sRBCs: sheep red blood cells; TEM: Transmission electron microscopy; RBCM: red blood cell membrane; SDS-PAGE: sodium dodecyl sulfate–polyacrylamide gel electrophoresis; NC membrane: nitrocellulose membrane; SDS-AGE: dodecyl sulfate agarose gel electrophoresis; MDBK cells: Madin–Darby bovine kidney cells; RPMI-1640 medium: Roswell Park Memorial Institute-1640 medium; FBS: fetal bovine serum; BMDMs: bone marrow-derived macrophages; TNF-α: tumor necrosis factor α; IL-1β: interleukin-1β; IFN-γ: interferon-γ; TGF-β: transforming growth factor-β; ELISA: enzyme-linked immunosorbent assay

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Pneumolysin Mediates Platelet Activation In Vitro

Cited by 35 publications

References 24 publications

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

Pneumonia as a cardiovascular disease

Replacing the 238th aspartic acid with an arginine impaired the oligomerization activity and inflammation-inducing property of pyolysin

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