Pneumolysin: A multifunctional pneumococcal virulence factor

Rubins, Jeffrey B.; Janoff, Edward N.

doi:10.1016/s0022-2143(98)90073-7

Cited by 73 publications

(65 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, Ply interactions with alveolar epithelial cells and pulmonary endothelial cells probably cause alveolar edema and hemorrhage during pneumococcal pneumonia. Ply action during pneumococcal infection disrupts the alveolar-capillary boundary, which produces an alveolar flooding providing nutrients for bacterial growth and facilitates penetration through the epithelium into the pulmonary interstitium and ultimately into the bloodstream (132). The cytotoxic effects of pneumolysin can directly inhibit phagocyte and immune cell function, which leads to suppression of the host inflammatory and immune responses.…”

Section: Pneumolysinmentioning

confidence: 99%

“…The cytotoxic effects of pneumolysin can directly inhibit phagocyte and immune cell function, which leads to suppression of the host inflammatory and immune responses. Low concentrations of Ply are able to inhibit human neutrophil and monocyte respiratory bursts, chemotaxis, bactericidal activity, and production of lymphokines and immunoglobulins (132). The virulence and multiple function of pneumolysin, especially in early stages of infection by pneumococci, are crucial to the pneumococcal colonization of a host.…”

Section: Pneumolysinmentioning

confidence: 99%

“…The method used to construct this figure and the color coding used are the same as in Fig. 4 (132). The presence of cholesterol in the target membrane is absolutely necessary for the cytotoxicity of CDCs, and Ply is no exception.…”

Section: Cholesterol-dependent Cytolysinsmentioning

confidence: 99%

“…This release of Ply from the cytoplasm is dependent on another S. pneumoniae enzyme, autolysin (LytA). Autolysin naturally degrades the bacterial cell wall during cell division, but under certain conditions such as in the stationary phase of growth in vitro or on antibiotic or detergent treatment it induces cell lysis (132). The details of the process of autolysis during infection are still under investigation and are not totally clear.…”

Section: Cholesterol-dependent Cytolysinsmentioning

confidence: 99%

See 3 more Smart Citations

Pneumococcal Virulence Factors: Structure and Function

Jedrzejas

2001

Microbiol Mol Biol Rev

407

354

View full text Add to dashboard Cite

The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease

show abstract

Section: Pneumolysinmentioning

confidence: 99%

Section: Pneumolysinmentioning

confidence: 99%

Section: Cholesterol-dependent Cytolysinsmentioning

confidence: 99%

Section: Cholesterol-dependent Cytolysinsmentioning

confidence: 99%

See 2 more Smart Citations

Pneumococcal Virulence Factors: Structure and Function

Jedrzejas

2001

Microbiol Mol Biol Rev

407

354

View full text Add to dashboard Cite

show abstract

“…The strains HB565 (encapsulated, Hic-positive), PR218 (unencapsulated, Hic-positive), and FP13 (unencapsulated, Hic-negative) were incubated with radiolabeled fH, SCR1-7, or SCR8 -20 (7,20, and 30 ng/reaction, respectively) and centrifuged through 20% sucrose. As shown in Fig.…”

Section: Binding Of Fh and Fh Recombinant Constructs To Pneumococcimentioning

confidence: 99%

Streptococcus pneumoniaeEvades Complement Attack and Opsonophagocytosis by Expressing thepspCLocus-Encoded Hic Protein That Binds to Short Consensus Repeats 8–11 of Factor H

Jarva

Janulczyk

Hellwage

et al. 2002

The Journal of Immunology

178

168

View full text Add to dashboard Cite

Streptococcus pneumoniae is an important cause of upper and lower respiratory tract infections, meningitis, peritonitis, bacterial arthritis, and sepsis. Here we have studied a novel immune evasion mechanism of serotype 3 pneumococci, which are particularly resistant to phagocytosis. On their surfaces the bacteria express the factor H-binding inhibitor of complement (Hic), a protein of the pneumococcal surface protein C family. Using radioligand binding, microtiter plate assays, surface plasmon resonance analysis, and recombinant constructs of factor H, we located the binding site of Hic to short consensus repeats (SCRs) 8–11 in the middle part of factor H. This represents a novel microbial interaction region on factor H. The only other ligand known so far for SCRs 8–11 of factor H is C-reactive protein (CRP), an acute phase protein that binds to the pneumococcal C-polysaccharide. The binding sites of Hic and CRP within the SCR8–11 region were different, however, because CRP did not inhibit the binding of Hic and required calcium for binding. Binding of factor H to Hic-expressing pneumococci promoted factor I-mediated cleavage of C3b and restricted phagocytosis of pneumococci. Thus, virulent pneumococci avoid complement attack and opsonophagocytosis by recruiting functionally active factor H with the Hic surface protein. Hic binds to a previously unrecognized microbial interaction site in the middle part of factor H.

show abstract

Physical Characterization and Formulation Development of a Recombinant Pneumolysoid Protein-Based Pneumococcal Vaccine

Joshi

Liyanage

et al. 2013

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Pneumolysin: A multifunctional pneumococcal virulence factor

Cited by 73 publications

References 51 publications

Pneumococcal Virulence Factors: Structure and Function

Pneumococcal Virulence Factors: Structure and Function

Streptococcus pneumoniaeEvades Complement Attack and Opsonophagocytosis by Expressing thepspCLocus-Encoded Hic Protein That Binds to Short Consensus Repeats 8–11 of Factor H

Physical Characterization and Formulation Development of a Recombinant Pneumolysoid Protein-Based Pneumococcal Vaccine

Contact Info

Product

Resources

About