China 
Africa 
Explore chapters and articles related to this topic
Bacteriology of Ophthalmic Infections
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
Arumugam Priya, Shunmugiah Karutha Pandian
Pneumolysin (PLY) is a potent 53 KDa pore-forming cytotoxin synthesized and located in the cytoplasm of pneumococci. Release of this toxin occurs immediately after spontaneous autolysis of the bacterial cell. Upon release, they interact with the cholesterol and bind the lipid bilayer followed by transmembrane pore formation and lysis of the cell. The pore-forming ability of the PLY can potentially disrupt the corneal epithelium upon infection. In addition to the cytotoxic property, it can directly activate the classical complement system. Activation of complement can either result in production of chemotactic molecules or direct the complement-mediated membrane attack on the host cell. The initiation of proinflammatory cytokines will mediate inflammation and tissue damage. Hence, the release of PLY on the corneal surface eventually leads to corneal ulceration followed by keratitis (Paton, 1996).
Telithromycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Eric Wenzler, Keith A. Rodvold
In addition to their antimicrobial activity, macrolides and ketolides have demonstrated many pleiotropic effects, including those arising from immunomodulatory and anti-inflammatory properties. These properties include inhibition of the production of the streptococcal toxin pneumolysin. This activity is clearly independent of the antibacterial activity as it has been demonstrated at sub-MIC concentrations and with strains of S. pneumoniae that are macrolide-resistant (Anderson et al., 2007).
Streptococcus pneumoniae
Published in Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward, Case Studies in Infectious Disease, 2010
Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward
The most important component of the S. pneumoniae outer surface is the polysaccharide capsule, since this is the principal virulence determinant of the bacterium. The capsule impedes phagocytosis primarily by inhibiting deposition of the opsonic complement component, C3b, on the bacterial surface thus impairing the immune response to S. pneumoniae. The structure of the capsule is complex and there are some 91 distinct antigenic types. S. pneumoniae has a typical gram-positive-type cell wall that features six layers of peptidoglycan with covalently bound teichoic acid (C-polysaccharide) and cell membrane-anchored lipoteichoic acid (Forssman antigen) (Figure 5). Both forms of teichoic acid have identical carbohydrate structures and contain choline. Although the vast majority of the teichoic acid is covered by the capsule, anti-phosphocholine antibody can protect against experimental pneumococcal infection and the acute phase reactant, C-reactive protein, can interact with choline residues in the cell wall. On the outer surface of the cell wall is a family of 12 choline-binding proteins (CBPs) that are noncovalently bound to the phosphorylcholine moiety of the wall. These include: the major autolysin of the pneumococcus, LytA; two other cell wall hydrolases, LytB and LytC, suggested to be involved in daughter cell separation as well as in bacterial uptake of DNA; PcpA, which is thought to be involved in protein–protein and protein–lipid interactions; PspA that decreases complement deposition on the bacterial surface during sepsis; and CbpA (SpsA), the most abundant of the CBPs, that functions as a cell-surface adhesin in the nasopharynx. CbpA has been shown to bind the secretory component of IgA and the complement component, C3. The pneumococcus contains a cholesterol-dependent pore-forming cytotoxin termed pneumolysin, which is stored intracellularly in most strains and is released upon cell lysis mediated by LytA. This toxin is important in the causation of meningitis because it damages ependymal cilia that line the ventricles of the brain and induces brain cells to undergo apoptosis. Also, H2O2 produced by the pneumococcus is a potent hemolysin. Finally, the bacterium secretes an IgA1 protease, which is able to subvert the activity of IgA1 by cleaving the molecule at the hinge region, and a neuraminidase that cleaves terminal sialic acid from glycoconjugates thereby uncovering epitopes for pneumococcal adherence.
The long search for a serotype independent pneumococcal vaccine
Published in Expert Review of Vaccines, 2020
T.R. Converso, L. Assoni, G.O. André, M. Darrieux, L.C.C. Leite
The search for vaccines against pneumococcal diseases began soon after the identification of the bacteria as the etiologic agent of pneumonia and other important infectious diseases; the high immunogenicity of the polysaccharide capsule, besides its role in virulence made it an evident choice as a vaccine antigen. Therefore, the first pneumococcal vaccine licensed in 1976 was a mixture of polysaccharides of prevalent serotypes, initially a 14-valent vaccine, PPSV-14, which was soon replaced by PPSV-23 in 1983. It is interesting that early on, protein antigens identified as virulence factors were also investigated as vaccine antigens. The pore-forming pneumolysin was one of the first antigens identified in S. pneumoniae due to its hemolytic properties (1977); however, its protective potential only became evident in 1983 [20,110]. Furthermore, it was extremely conserved and found in virtually all identified pneumococci. Due to its cytotoxicity, a variety of genetic mutations have been developed and evaluated as vaccine candidates [111,112]. PdA/B, PdT, and PlyD1, have different mutations, varying degrees of detoxification and immunogenicity [112]. A chemically detoxified derivative has also been studied, dPly, which has been included in several pneumococcal formulations of serotype-independent vaccines tested in phase I and II clinical trials [45,46] (Figure 1, Table 1). Pneumolysin and its derived molecules have been evaluated in pre-clinical and clinical trials for longer than any polysaccharide-based vaccine.
A Novel PspA Protein Vaccine Intranasal Delivered by Bacterium-Like Particles Provides Broad Protection Against Pneumococcal Pneumonia in Mice
Published in Immunological Investigations, 2018
Dandan Wang, Jingcai Lu, Jinfei Yu, Hongjia Hou, Kees Leenhouts, Maarten L. Van Roosmalen, Tiejun Gu, Chunlai Jiang, Wei Kong, Yongge Wu
In this study, we showed that immunization with PspA (family 2 clade 4) delivered by BLPs could protect against pneumococcal challenges by strains of different PspA families. Superior cross-protection was demonstrated against challenge with two different pneumococcal PspA family strains when compared with PPV23. Additionally, the challenge pneumococcal strains ATCC6303 and ATCC10813 belong to different PspA families and clades but have the same serotype (serotype 3). This fact likely indicates that the broad-spectrum protection was only related to PspA, and it was not associated with serotype. We also believe that developing hybrid vaccines is necessary. Over the years, a number of other pneumococcal proteins have been evaluated as candidate antigens for protein-based vaccines (Ogunniyi et al., 2007), such as pneumolysin (Ply), pneumococcal surface adhesin A (PsaA), and pneumococcal surface protein C (PspC). Each of these proteins showed the potential to be combined with PspA in mucosal vaccines. Specifically, the immunogenicity and protection of Ply and PsaA-PspA have been confirmed in our previous studies (Lu et al., 2014, 2015). In future work, we would like to introduce additional pneumococcal proteins to BLPs to develop a multivalent mucosal vaccine.
Platelet interaction with bacterial toxins and secreted products
Published in Platelets, 2015
This family of toxins target the cell membrane and disrupt membrane function. The primary result is cell lysis and death. Staphylococcus aureus α-toxin is a pore-forming toxin with a broad range of tissue specificity. The toxin disrupts barrier function in the skin, lungs and vasculature, thereby contributing to the pathogenesis of diverse S. aureus infections [45]. As early as 1964 it was reported that α-toxin stimulated platelet aggregation [46]. Platelet activation in response to α-toxin led to enhanced platelet procoagulant response, in the absence of platelet lysis [47, 48]. Kraemer et al. have reported a direct toxic effect of S. aureus α-toxin and E. coli α-toxin on platelets by the induction of apoptosis [49]. Recent reports have confirmed that the treatment of platelets with α-toxin generates immediate responses in the form of platelet activation, aggregation and PNC formation, and also prolonged effects through initiation of protein synthesis [50–52]. The mechanism involved in generating platelet activation in response to this membrane-disrupting toxin has not been clarified. Pneumolysin is a pore-forming toxin and important virulence factor for Streptococcus pneumoniae. The toxin has been reported to mediate human platelet lysis [53]. Recently, Keane et al. reported that S. pneumonia bacteria stimulate platelet aggregation; however, this was not dependent on pneumolysin production by the bacteria [54].