Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface

Ren, Bin; Szalai, Alexander J.; Hollingshead, Susan K.; Briles, David E.

doi:10.1128/iai.72.1.114-122.2004

Cited by 173 publications

(173 citation statements)

References 36 publications

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“…In S. mutans , VicR Sm negatively regulates pepO and SMU _ 399 , which encode proteases implicated in evasion of complement system [118]. In addition, VicRK Spn regulates pspA [105], which encodes a species-specific surface protein (PspA) involved in complement evasion [128]. In S. mutans , VicR Sm also directly represses genes involved in competence and competence-induced bacteriocin ( comCDE and nlmC ) [113], and copY [117], part of the copYAZ operon required for copper homeostasis and regulation of membrane potential, competence, and biofilm formation [129].…”

Section: Vicrk Regulons Of Tcss Are Diverse and Species-specificmentioning

confidence: 99%

Two-component signal transduction systems in oral bacteria

Mattos-Graner

Duncan²

2017

Journal of Oral Microbiology

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We present an overview of how members of the oral microbiota respond to their environment by regulating gene expression through two-component signal transduction systems (TCSs) to support conditions compatible with homeostasis in oral biofilms or drive the equilibrium toward dysbiosis in response to environmental changes. Using studies on the sub-gingival Gram-negative anaerobe Porphyromonas gingivalis and Gram-positive streptococci as examples, we focus on the molecular mechanisms involved in activation of TCS and species specificities of TCS regulons.

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Section: Vicrk Regulons Of Tcss Are Diverse and Species-specificmentioning

confidence: 99%

Two-component signal transduction systems in oral bacteria

Mattos-Graner

Duncan²

2017

Journal of Oral Microbiology

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“…A capsular type 3 pneumococcal strain (WU2, PspA ϩ ) (24,25) and its isogenic mutant (JY1119, PspA Ϫ ) (4,7,26) were used. Bacterial stocks were frozen at Ϫ80°C in Todd-Hewitt broth supplemented with 0.5% yeast extract containing 10% glycerol.…”

Section: Bacteria and Infectionsmentioning

confidence: 99%

The Virulence Function of Streptococcus pneumoniae Surface Protein A Involves Inhibition of Complement Activation and Impairment of Complement Receptor-Mediated Protection

Ren¹,

McCrory

Pass

et al. 2004

The Journal of Immunology

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107

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Complement is important for elimination of invasive microbes from the host, an action achieved largely through interaction of complement-decorated pathogens with various complement receptors (CR) on phagocytes. Pneumococcal surface protein A (PspA) has been shown to interfere with complement deposition onto pneumococci, but to date the impact of PspA on CR-mediated host defense is unknown. To gauge the contribution of CRs to host defense against pneumococci and to decipher the impact of PspA on CR-dependent host defense, wild-type C57BL/6J mice and mutant mice lacking CR types 1 and 2 (CR1/2−/−), CR3 (CR3−/−), or CR4 (CR4−/−) were challenged with WU2, a PspA+ capsular serotype 3 pneumococcus, and its PspA− mutant JY1119. Pneumococci also were used to challenge factor D-deficient (FD−/−), LFA-1-deficient (LFA-1−/−), and CD18-deficient (CD18−/−) mice. We found that FD−/−, CR3−/−, and CR4−/− mice had significantly decreased longevity and survival rate upon infection with WU2. In comparison, PspA− pneumococci were virulent only in FD−/− and CR1/2−/− mice. Normal mouse serum supported more C3 deposition on pneumococci than FD−/− serum, and more iC3b was deposited onto the PspA− than the PspA+ strain. The combined results confirm earlier conclusions that the alternative pathway of complement activation is indispensable for innate immunity against pneumococcal infection and that PspA interferes with the protective role of the alternative pathway. Our new results suggest that complement receptors CR1/2, CR3, and CR4 all play important roles in host defense against pneumococcal infection.

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“…The main function of PspA is preventing the deposition of complement on the surface of the bacterium thereby inhibiting opsonization and phagocytosis (Ren et al, 2004a;Ren et al, 2004b). PspA was also shown to inhibit death by apolactoferrin at mucosal sites (Shaper et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Kunda

Alfagih

Miyaji

et al. 2015

International Journal of Pharmaceutics

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Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immune compromised, the very young and the old, and remains one of the leading causes of death.A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in L-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ~150 nm and achieved ~ 20 µg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31±1.32% and MMAD of 1.70±0.03 μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA.

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Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface

Cited by 173 publications

References 36 publications

Two-component signal transduction systems in oral bacteria

Two-component signal transduction systems in oral bacteria

The Virulence Function of Streptococcus pneumoniae Surface Protein A Involves Inhibition of Complement Activation and Impairment of Complement Receptor-Mediated Protection

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

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