Immunization with Pneumolysin Protects Against Both Retinal and Global Damage Caused by<i>Streptococcus pneumoniae</i>Endophthalmitis

Sanders, Melissa E.; Norcross, Erin W.; Moore, Quincy C.; Fratkin, Jonathan D.; Thompson, Hilary W.; Marquart, Mary E.

doi:10.1089/jop.2010.0077

Cited by 18 publications

(35 citation statements)

References 30 publications

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“…Several PFTs have been shown to be immunogenic, such as S. pneumoniae PLY, S. aureus alpha-toxin, M. tuberculosis ESAT-6, and L. monocytogenes LLO (370)(371)(372)(373), but detailed studies on specific effects of PFTs on the adaptive immune system are scarce.…”

Section: Adaptive Immune Responses To Pftsmentioning

confidence: 99%

“…PFTs may be viable targets for vaccination against bacterial infection, as observed, for instance, for S. pneumoniae, S. aureus, M. tuberculosis, and L. monocytogenes (370)(371)(372)(373). Although active immunization against ALO protected mice from purified ALO, it did not protect them from B. anthracis infection (474).…”

Section: Pfts As Targets For Antimicrobial Prophylactics and Therapeumentioning

confidence: 99%

See 1 more Smart Citation

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Los

Randis

Aroian

et al. 2013

Microbiol Mol Biol Rev

344

351

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SUMMARY Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae , group A and B streptococci, Staphylococcus aureus , Escherichia coli , and Mycobacterium tuberculosis . PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo . This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.

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Section: Adaptive Immune Responses To Pftsmentioning

confidence: 99%

Section: Pfts As Targets For Antimicrobial Prophylactics and Therapeumentioning

confidence: 99%

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Los

Randis

Aroian

et al. 2013

Microbiol Mol Biol Rev

344

351

View full text Add to dashboard Cite

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“…The mechanisms underlying this effect were not reported. Based on the report of pneumolysin as an important virulence determinant of S. pneumoniae endophthalmitis in rats (Ng et al, 1997; Ng et al, 2002), Sanders et al (2010) used the rabbit model to demonstrate the efficacy of immunizing with pneumolysin in protecting the retina from damage during S. pneumoniae endophthalmitis. Although these neutralization strategies are not currently used in therapy, these studies further support the importance of bacterial toxins as potential targets for the treatment of endophthalmitis.…”

Section: Experimental Models: Therapeutics and Virulencementioning

confidence: 99%

Modeling intraocular bacterial infections

Astley

Coburn

Parkunan

et al. 2016

Progress in Retinal and Eye Research

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Bacterial endophthalmitis is an infection and inflammation of the posterior segment of the eye which can result in significant loss of visual acuity. Even with prompt antibiotic, anti-inflammatory and surgical intervention, vision and even the eye itself may be lost. For the past century, experimental animal models have been used to examine various aspects of the pathogenesis and pathophysiology of bacterial endophthalmitis, to further the development of anti-inflammatory treatment strategies, and to evaluate the pharmacokinetics and efficacies of antibiotics. Experimental models allow independent control of many parameters of infection and facilitate systematic examination of infection outcomes. While no single animal model perfectly reproduces the human pathology of bacterial endophthalmitis, investigators have successfully used these models to understand the infectious process and the host response, and have provided new information regarding therapeutic options for the treatment of bacterial endophthalmitis. This review highlights experimental animal models of endophthalmitis and correlates this information with the clinical setting. The goal is to identify knowledge gaps that may be addressed in future experimental and clinical studies focused on improvements in the therapeutic preservation of vision during and after this disease.

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“…This model mimics the infection course after introduction of bacteria directly into the posterior segment of the eye that would occur following a surgical procedure or penetrating injury, but does not allow for the analysis of host immunological status and bacterial factors that contribute to the development of EE. This model system allows intravitreal injection across the pars plana of low inocula that allow the bacterium under study to adapt to the intraocular environment of the eye and replicate (Booth et al, 1995;Booth et al, 1997;Callegan et al, 1999a;Jett et al, 1992;Sanders et al, 2010;Sanders et al, 2011). Depending on the infecting organisms, infection symptoms in the rabbit model develop over a period ranging from 6 hours to 3 days, and a number of infection parameters can be repeatedly monitored and quantitative data obtained.…”

Section: Experimental Endophthalmitis and The Roles Of Bacterial And mentioning

confidence: 99%

“…Infection with an isogenic unencapsulated S. pneumoniae mutant strain resulted in significantly lower slit lamp examination scores, significantly greater retinal function, and significantly less neutrophil infiltration into the eye compared with the wildtype parental strain in this model. Moreover, they demonstrated the efficacy of immunizing with the S. pneumoniae pneumolysin in protecting the eye from retinal damage during S. pneumoniae endophthalmitis (Sanders et al, 2010). In summary, the rabbit model of experimental endophthalmitis has proven invaluable in assessing the role of bacterial virulence factors and identifiying potentially new therapeutic targets.…”

Section: Experimental Endophthalmitis and The Roles Of Bacterial And mentioning

confidence: 99%