Protection fromStreptococcus pneumoniaeKeratitis by Passive Immunization with Pneumolysin Antiserum

Green, Sherrina N.; Sanders, Melissa E.; Moore, Quincy C.; Norcross, Erin W.; Monds, K.S.; Caballero, Armando R.; McDaniel, Larry S.; Robinson, Sherrina A.; Onwubiko, Chinwendu; O’Callaghan, Richard J.; Marquart, Mary E.

doi:10.1167/iovs.07-0492

Cited by 14 publications

(20 citation statements)

References 23 publications

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“…Furthermore, the pneumococcus faces unfavorable growth conditions in the cornea, which would cause the bacteria to release autolysin and die [24] . This occurrence of pneumococcal death is not a new phenomenon, according to Johnson et al [16] and Green et al [17] , who demonstrated pneumococcal keratitis in rabbits. Both studies found that by 48 h after infection, bacteria were cleared from most of the corneas.…”

Section: Discussionmentioning

confidence: 94%

“…The corneal damage observed in pneumococcal keratitis has been attributed mainly to pneumococcal virulence factors, such as the toxin pneumolysin, that initiate a robust immune response [14][15][16] . Previous studies have reported pneumococcal keratitis in the rabbit model [14,[17][18][19] . The rabbit has served as an appropriate model to study bacterial virulence factors, host effects such as inflammation, antibiotic treatments and the testing of novel therapies.…”

Section: Development Of a Streptococcus Pneumoniae Keratitis Model Inmentioning

confidence: 98%

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Development of a Streptococcus pneumoniae Keratitis Model in Mice

Moore¹,

McCormick²,

Norcross³

et al. 2009

Ophthalmic Res

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Background:Streptococcus pneumoniae is a common cause of bacterial keratitis, and models to examine the ocular pathogenesis of this bacterium would aid in efforts to treat pneumococcal keratitis. The aim of this study was to establish a murine model of pneumococcal keratitis. Methods: The corneas of A/J, BALB/c or C57BL/6 mice were scratched and topically infected with a clinical strain of S. pneumoniae. Slitlamp examination (SLE), enumeration of bacteria in the corneas and histology were performed. Results: Bacteria were recovered from the eyes of A/J mice on postinfection (PI) days 1 [1.96 ± 0.61 log₁₀ colony-forming units (CFU)] and 3 (1.41 ± 0.71 log₁₀ CFU). SLE scores were significantly higher in the infected A/J mice as compared to the BALB/c or C57BL/6 mice on PI day 3 (p < 0.0001) and steadily increased over time, reaching a maximal value of 3.00 ± 0.35 on PI day 10. Histopathology revealed stromal edema and the influx of polymorphonuclear leukocytes on PI days 7 and 10, and corneal disruption on PI day 7. Conclusions:S. pneumoniae keratitis was established in A/J mice, but not BALB/c or C57BL/6 mice.

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Section: Discussionmentioning

confidence: 94%

Section: Development Of a Streptococcus Pneumoniae Keratitis Model Inmentioning

confidence: 98%

Development of a Streptococcus pneumoniae Keratitis Model in Mice

Moore¹,

McCormick²,

Norcross³

et al. 2009

Ophthalmic Res

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“…In addition to being a major cause of hospital-acquired infections, such as ventilator-associated pneumonia (4,5), Serratia marcescens is a common cause of MK (1,2,(6)(7)(8), yet the virulence factors involved in this process are poorly understood. In general, bacterial secreted factors, including hemolysins and proteases, contribute to the pathogenesis of bacterial corneal infections (9)(10)(11)(12). There are several studies characterizing the importance of proteases from S. marcescens isolates in ocular infections, most recently reviewed by Matsumoto (13).…”

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confidence: 99%

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

et al. 2015

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The Gram-negative bacterium and opportunistic pathogen Serratia marcescens causes ocular infections in healthy individuals. Secreted protease activity was characterized from 44 ocular clinical isolates, and a higher frequency of protease-positive strains was observed among keratitis isolates than among conjunctivitis isolates. A positive correlation between protease activity and cytotoxicity to human corneal epithelial cells in vitro was determined. Deletion of prtS in clinical keratitis isolate K904 reduced, but did not eliminate, cytotoxicity and secreted protease production. This indicated that PrtS is necessary for full cytotoxicity to ocular cells and implied the existence of another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the S. marcescens Db11 genome revealed three additional open reading frames predicted to code for serralysin-like proteases noted here as slpB, slpC, and slpD. Induced expression of prtS and slpB, but not slpC and slpD, in strain PIC3611 rendered the strain cytotoxic to a lung carcinoma cell line; however, only prtS induction was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion of both prtS and slpB genes was defective in secreted protease activity and cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI-inhibited protease activity and cytotoxicity to airway and ocular cell lines in vitro. Lastly, genetic analysis indicated that the type I secretion system gene, lipD, is required for SlpB secretion. These genetic data introduce SlpB as a new cytotoxic protease from S. marcescens. Microbial keratitis (MK) is a blinding disease with poor visual outcomes even with effective antibiotics and antifungal agents (1-3). In addition to being a major cause of hospital-acquired infections, such as ventilator-associated pneumonia (4, 5), Serratia marcescens is a common cause of MK (1, 2, 6-8), yet the virulence factors involved in this process are poorly understood. In general, bacterial secreted factors, including hemolysins and proteases, contribute to the pathogenesis of bacterial corneal infections (9-12). There are several studies characterizing the importance of proteases from S. marcescens isolates in ocular infections, most recently reviewed by Matsumoto (13). Serralysin is a cytotoxic factor capable of killing mammalian cells in vitro (14,15). Purified serralysin is sufficient to cause keratitis when injected into rabbit eyes and promotes the spread of bacteria through the corneal stroma (16-18). Additionally, serralysin can degrade components of the human immune system, such as PAR-2, in vitro, and this may impact corneal pathogenesis (13,(19)(20)(21). Serralysin, and serralysin family metalloproteases, such as alkaline protease from Pseudomonas aeruginosa, can proteolyze mammalian cell surface proteins, thereby modulating cell physiology. A recent example is the protease-mediated activation of the epithelial sodium channel, lea...

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“…24 In addition, when rabbits infected with S. pneumoniae WU2 were passively immunized with anti-PLY sera, there was no difference in recovered CFUs, although there was a decrease in the clinical scores of the passively immunized group. 30 It should be noted that Freund's complete adjuvant was used in the initial immunizations for all the groups regardless of immunogen. Freund's complete adjuvant contains multiple mycobacterial cell components and has been reported to elicit a variety of responses in host animal species ranging from the characteristic tubercle skin lesions to changes in delayed type hypersensitivity (for review, see Ref.…”

Section: Discussionmentioning

confidence: 99%

“…Corneas of rabbits passively immunized exhibited significantly reduced pathology during the course of the infection and showed protection for as long as 14 days after infection. 30 The purpose of the present study was to determine the extent of protection conferred to rabbits during pneumococcal keratitis when actively immunized against S. pneumoniae polysaccharide capsule (PPSV23) or PLY and to determine the protective value of anti-PLY antibody on human corneal epithelial cells. We determined that active immunization against PLY mixed with Freund's adjuvant provided significant protection against corneal inflammation associated with pneumococcal keratitis.…”

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confidence: 99%

Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine forStreptococcus pneumoniaeKeratitis

Norcross

Sanders

Moore

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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Active immunization with pneumococcal capsular polysaccharide and Freund's adjuvant fails to produce opsonizing antibodies, and passive administration of serotype specific opsonizing antibodies offers no protection against pneumococcal keratitis in the rabbit, whereas active immunization with the conserved protein virulence factor PLY and Freund's adjuvant is able to reduce corneal inflammation associated with pneumococcal keratitis, but has variable effects on bacterial loads in the cornea.

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Protection fromStreptococcus pneumoniaeKeratitis by Passive Immunization with Pneumolysin Antiserum

Abstract: HI-PLY and psiPLY both elicit antibodies that provide passive protection against S. pneumoniae keratitis.

Cited by 14 publications

References 23 publications

Development of a <i>Streptococcus pneumoniae </i>Keratitis Model in Mice

Development of a <i>Streptococcus pneumoniae </i>Keratitis Model in Mice

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine forStreptococcus pneumoniaeKeratitis

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