Activation of human complement by the pneumococcal toxin pneumolysin

Paton, James C.; Rowan-Kelly, B; Fèrrante, Antonio

doi:10.1128/iai.43.3.1085-1087.1984

Cited by 194 publications

(75 citation statements)

References 15 publications

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“…As has now been demonstrated for PLO, TACYs play an important role in the pathogenesis of the bacteria which express them. Pneumolysin (PLY), expressed by S. pneumoniae, activates complement (38), stimulates host cytokine production (19), and inhibits the respiratory burst and bacteriocidal activity of neutrophils (37) and monocytes (34). Not surprisingly, insertional activation of the gene encoding PLY results in a significant decrease in virulence in a mouse model (5).…”

Section: Discussionmentioning

confidence: 99%

An Arcanobacterium(Actinomyces) pyogenes Mutant Deficient in Production of the Pore-Forming Cytolysin Pyolysin Has Reduced Virulence

1999

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Pyolysin (PLO), the hemolytic exotoxin expressed by Arcanobacterium (Actinomyces) pyogenes, is a member of the thiol-activated cytolysin family of bacterial toxins. Insertional inactivation of the plo gene results in loss of expression of PLO with a concomitant loss in hemolytic activity. The plo mutant, PLO-1, has an approximately 1.8-log 10 reduction in the 50% infectious dose compared to that for wild-type A. pyogenes in a mouse intraperitoneal infection model. Studies involving cochallenge of wild-type and PLO-1 bacteria resulted in recovery of similar numbers of both strains, suggesting that PLO production is required for survival in vivo. Recombinant, His-tagged PLO (His-PLO) is cytotoxic for mouse peritoneal macrophages and J774 cells in a dose-dependent manner. Protection against challenge with A. pyogenes could be afforded by vaccination with formalin-inactivated His-PLO, suggesting that PLO is a host-protective antigen, as well as a virulence determinant.

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Section: Discussionmentioning

confidence: 99%

An Arcanobacterium(Actinomyces) pyogenes Mutant Deficient in Production of the Pore-Forming Cytolysin Pyolysin Has Reduced Virulence

1999

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“…Along such lines, antibodies against pneumolysin have been demonstrated to protect against cell death in vitro and diminish the tissue damage that occurs during severe pneumococcal disease [49]. Pneumolysin also has other activities, such as activation of the classical complement cascade and binding to Toll-like receptor 4 to trigger inflammation [50,51]. Presumably, antibodies that block these interactions would also reduce the inflammatory damage that occurs during infection [51].…”

Section: Multi-modal Protection: Prevention Of Disseminated Disease Amentioning

confidence: 99%

Opening the OPK Assay Gatekeeper: Harnessing Multi-Modal Protection by Pneumococcal Vaccines

et al. 2019

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Pneumococcal vaccine development is driven by the achievement of high activity in a single gatekeeper assay: the bacterial opsonophagocytic killing (OPK) assay. New evidence challenges the dogma that anti-capsular antibodies have only a single function that predicts success. The emerging concept of multi-modal protection presents an array of questions that are fundamental to adopting a new vaccine design process. If antibodies have hidden non-opsonic functions that are protective, should these be optimized for better vaccines? What would protein antigens add to protective activity? Are cellular immune functions additive to antibodies for success? Do different organs benefit from different modes of protection? Can vaccine activities beyond OPK protect the immunocompromised host? This commentary raises these issues at a time when capsule-only OPK assay-based vaccines are increasingly seen as a limiting strategy.

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“…In pneumococcal meningitis, the majority of the damage to the blood-brain barrier has been attributed to PLY (Zysk et al, 2001;Mitchell and Dalziel, 2014). Structural homology to the Fc region of immunoglobulin G (IgG) also allows PLY to activate the classical complement pathway away from intact bacteria to deplete host serum complement levels and promote survival and spread (Paton et al, 1984;Mitchell et al, 1991;Rossjohn et al, 1998;Alcantara et al, 2001). Recently, PLY was also shown to contribute to the assembly of pneumococcal biofilms (Shak et al, 2013).…”

Section: Pneumolysinmentioning

confidence: 99%

Streptococcal toxins: role in pathogenesis and disease

Barnett

Cole

Rivera-Hernandez

et al. 2015

Cellular Microbiology

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Summary Group A Streptococcus (Streptococcus pyogenes), group B Streptococcus (Streptococcus agalactiae) and Streptococcus pneumoniae (pneumococcus) are host‐adapted bacterial pathogens among the leading infectious causes of human morbidity and mortality. These microbes and related members of the genus Streptococcus produce an array of toxins that act against human cells or tissues, resulting in impaired immune responses and subversion of host physiological processes to benefit the invading microorganism. This toxin repertoire includes haemolysins, proteases, superantigens and other agents that ultimately enhance colonization and survival within the host and promote dissemination of the pathogen.

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Activation of human complement by the pneumococcal toxin pneumolysin

Cited by 194 publications

References 15 publications

An Arcanobacterium(Actinomyces) pyogenes Mutant Deficient in Production of the Pore-Forming Cytolysin Pyolysin Has Reduced Virulence

An Arcanobacterium(Actinomyces) pyogenes Mutant Deficient in Production of the Pore-Forming Cytolysin Pyolysin Has Reduced Virulence

Opening the OPK Assay Gatekeeper: Harnessing Multi-Modal Protection by Pneumococcal Vaccines

Streptococcal toxins: role in pathogenesis and disease

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