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Species specific diagnosis of Streptococcus pneumoniae infectionGillespie, S. H. January 1994 (has links)
No description available.
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Structure-Function Relationships of C-Reactive Protein in Bacterial InfectionNgwa, Donald N., Agrawal, Alok 01 January 2019 (has links)
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. One host defense function of C-reactive protein (CRP) is to protect against Streptococcus pneumoniae infection as shown by experiments employing murine models of pneumococcal infection. The protective effect of CRP is due to reduction in bacteremia. There is a distinct relationship between the structure of CRP and its anti-pneumococcal function. CRP is functional in both native and non-native pentameric structural conformations. In the native conformation, CRP binds to pneumococci through the phosphocholine molecules present on the C-polysaccharide of the pneumococcus and the anti-pneumococcal function probably involves the known ability of ligand-complexed CRP to activate the complement system. In the native structure-function relationship, CRP is protective only when given to mice within a few hours of the administration of pneumococci. The non-native pentameric conformation of CRP is created when CRP is exposed to conditions mimicking inflammatory microenvironments, such as acidic pH and redox conditions. In the non-native conformation, CRP binds to immobilized complement inhibitor factor H in addition to being able to bind to phosphocholine. Recent data using CRP mutants suggest that the factor H-binding function of non-native CRP is beneficial: in the non-native structure-function relationship, CRP can be given to mice any time after the administration of pneumococci irrespective of whether the pneumococci became complement-resistant or not. In conclusion, while native CRP is protective only against early stage infection, non-native CRP is protective against both early stage and late stage infections. Because non-native CRP displays phosphocholine-independent anti-pneumococcal activity, it is quite possible that CRP functions as a general anti-bacterial molecule.
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Comparison of Anti-Pneumococcal Functions of Native and Modified Forms of C-Reactive ProteinNgwa, Donald Neba 01 May 2016 (has links)
The anti-pneumococcal function of native C-reactive protein (CRP) involves its binding to phosphocholine molecules present on Streptococcus pneumoniae and subsequent activation of the complement system. However, when pneumococci recruit complement inhibitory protein factor H on their surface, they escape complement attack. Non-native forms of CRP have been shown to bind immobilized factor H. Accordingly, we hypothesized that modified CRP would bind to factor H on pneumococci, masking its complement inhibitory activity, allowing native CRP to exert its anti-pneumococcal function. As reported previously, native CRP protected mice from lethal pneumococcal infection when injected 30 minutes before infection but not when injected 24 hours after infection. However, a combination of native and mutant CRP was found to protect mice even when administered 24 hours after infection. Therefore, it is concluded that while native CRP is protective only against early-stage infection, a combination of native and mutant CRP offers protection against late-stage infection.
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A Novel Mode of Action of C-reactive Protein in Protecting Against Streptococcus pneumoniae Infection and Synergy with AntibioticsNgwa, Donald 01 May 2020 (has links)
C-reactive protein (CRP) is a part of the innate immune system, is synthesized in the liver, its blood level increases in inflammatory states, and it binds to Streptococcus pneumoniae. The conformation of CRP is altered under conditions mimicking an inflammatory milieu and this non-native CRP also binds to immobilized/aggregated/pathogenic proteins. Experiments in mice have revealed that one of the functions of CRP is to protect against pneumococcal infection. For protection, CRP must be injected into mice within two hours of administering pneumococci, thus, CRP is protective against early-stage infection but not against late-stage infection. It is unknown how CRP protects or why CRP does not protect against late-stage infection. The hypotheses are that the protection requires complement activation by CRP-pneumococci complexes and that CRP cannot protect if pneumococci have time to recruit complement inhibitor factor H on their surface to become complement attack-resistant. To test these hypotheses, we generated CRP mutants by site-directed mutagenesis: a mutant that binds to pneumococci but does not activate complement and a mutant that binds to immobilized factor H. We found that mutant CRP incapable of activating complement was not protective against infection and that mutant CRP capable of binding to factor H was protective against both early and late stage infections. Additional experiments showed that CRP enhances the effects of the antibiotic clarithromycin in reducing bacteremia in infected mice. Moreover, we observed that mutant CRP capable of binding to factor H bound to several proteins immobilized on plastic, suggesting that CRP recognizes a pattern, probably an amyloid-like structure, on immobilized proteins. Indeed, mutant CRP, after binding to amyloid b peptides, prevented the formation of pathogenic amyloid fibrils. Lastly, employing a hepatic cell line, we investigated the mechanism of CRP expression in response to pro-inflammatory cytokines. We found that the transcription factor C/EBPb and two C/EBP-binding sites on the CRP promoter were critical for inducing CRP expression. We conclude that complement activation is necessary for CRP-mediated protection against infection, that CRP functions in two structural conformations, that CRP and clarithromycin act synergistically, that CRP has anti-amyloidogenic properties, and the increased CRP expression requires C/EBPb.
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Binding of the Monomeric Form of C-Reactive Protein to Enzymatically-Modified Low-Density Lipoprotein: Effects of PhosphoethanolamineSingh, Sanjay K., Suresh, Madathilparambil V., Hammond, David J., Rusiñol, Antonio E., Potempa, Lawrence A., Agrawal, Alok 11 August 2009 (has links)
Background: The 5 subunits of native pentameric C-reactive protein (CRP) are dissociated to generate the monomeric form of CRP (mCRP) in some in vitro conditions, both physiological and non-physiological, and also in vivo. Many bioactivities of mCRP generated by urea-treatment of CRP and of mCRP generated by mutating the primary structure of CRP have been reported. The bioactivities of mCRP generated by spontaneous dissociation of CRP are largely unexplored. Methods: We purified mCRP generated by spontaneous dissociation of CRP and investigated the binding of mCRP to enzymatically-modified low-density lipoprotein (E-LDL). Results: mCRP was approximately 60 times more potent than CRP in binding to E-LDL. In the presence of the small-molecule compound phosphoethanolamine (PEt), at 37 °C, the binding of mCRP to E-LDL was enhanced <2-fold, while the binding of CRP to E-LDL was enhanced >10-fold. In contrast, PEt inhibited the binding of both CRP and mCRP to pneumococcal C-polysaccharide, another phosphocholine-containing ligand to which CRP and mCRP were found to bind. We have not investigated yet whether PEt alters the structure of CRP at 37 °C. Conclusions: Combined data suggest that the targeting of CRP with the aim to monomerize CRP in vivo may be an effective approach to capture modified forms of LDL.
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