Pneumococcal Surface Protein C Contributes to Sepsis Caused by<i>Streptococcus pneumoniae</i>in Mice

Iannelli, Francesco; Chiavolini, Damiana; Ricci, Susanna; Oggioni, Marco R.; Pozzi, Gianni

doi:10.1128/iai.72.5.3077-3080.2004

Cited by 72 publications

(82 citation statements)

References 21 publications

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“…The recruitment of factor H to the surface of pneumococci efficiently prevents the activation of C3b and the complement-mediated opsonophagocytosis of pneumococci (46). The improved survival of pneumococci expressing PspC or Hic in a systemic mouse infection model and in microglial cells provides further evidence for the importance and versatility of PspC in different host niches (29,31). A recent study indicated that carriage isolates, which produce lesser amounts of CPS than the invasive isolates, recruit significantly more factor H than the systemic isolates (53).…”

Section: Discussionmentioning

confidence: 78%

“…The lack of PspC in the pneumococci of serotype 2 strain D39 and the lack of Hic in serotype 3 strain A66 attenuated pneumococcal virulence during sepsis. Apparently this defect results in decreased uptake by polymorphonuclear leukocytes (29,30). In addition, pneumococci deficient in PspC, but not wild-type pneumococci, are efficiently killed by microglia cells, which represent the resident phagocytes in the brain (31).…”

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confidence: 99%

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The Host Immune Regulator Factor H Interacts via Two Contact Sites with the PspC Protein of Streptococcus pneumoniae and Mediates Adhesion to Host Epithelial Cells

Hammerschmidt

Agarwal

Kunert

et al. 2007

The Journal of Immunology

124

139

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Pneumococcal surface protein C (PspC) of Streptococcus pneumoniae is a key virulence factor that mediates adhesion to host cells and immune evasion of the host complement. PspC binds the host immune and complement regulator factor H, which is composed of 20 short consensus repeats (SCR). This interaction contributes to pneumococcal virulence. In this study, we identified within the factor H protein two separate PspC binding regions, which were localized to SCR8–11 and SCR19–20, by using recombinant factor H deletion constructs for Western blotting assays and surface plasmon resonance studies. A detailed analysis of binding epitopes in these SCR by peptide spot arrays identified several linear binding regions within the sequences of SCR8–11 and SCR19–20. In addition, the factor H binding site was mapped within the pneumococcal PspC protein to a 121-aa-long stretch positioned in the N terminus (residues 38–158). Factor H attached to the surface of pneumococci via PspC significantly enhanced pneumococcal adherence to host epithelial and endothelial cells. This adhesion was specific and was blocked with a truncated N-terminal factor H-binding fragment of PspC. In conclusion, the acquisition of factor H by pneumococci via PspC occurs via two contact sites located in SCR8–11 and SCR19–20, and factor H attached to the surface of the pneumococcus promotes adhesion to both host epithelial and endothelial cells.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

The Host Immune Regulator Factor H Interacts via Two Contact Sites with the PspC Protein of Streptococcus pneumoniae and Mediates Adhesion to Host Epithelial Cells

Hammerschmidt

Agarwal

Kunert

et al. 2007

The Journal of Immunology

124

139

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“…This finding is also consistent with a recent study (Orihuela et al, 2004a) that demonstrated that CbpA is not required for the entry of pneumococci into the bloodstream from the lungs, nor for survival in the blood. On another note, CbpA has also been shown to interact with factor H and C3 (Dave et al, 2001;Janulczyk et al, 2000), and to be important in a mouse sepsis model (Iannelli et al, 2004), suggesting a dual role for CbpA in colonization (adherence) and in systemic disease. This might explain why in this study, the expression of cbpA was also significantly upregulated in the lungs and blood, compared to expression in vitro.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of key pneumococcal virulence genes in vivo

2006

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Few studies have examined in vivo virulence gene expression in Streptococcus pneumoniae. In this study, expression of key pneumococcal virulence genes cbpA, pspA, ply, psaA, cps2A, piaA, nanA and spxB in the nasopharynx, lungs and bloodstream of mice was investigated, following intranasal challenge with the serotype 2 strain D39. Bacterial RNA was extracted, linearly amplified and assayed by real-time RT-PCR. At 72 h, cbpA mRNA was present at higher levels in the nasopharynx and lungs than in the blood. At this time-point, the mRNAs for PspA and PiaA were most abundant in the nasopharynx, whereas no significant difference in gene expression between niches was observed for ply, psaA and cps2A. Both nanA and spxB mRNAs were present in higher amounts in the nasopharynx than in the lungs or blood. These findings illustrate the dynamic nature of pneumococcal virulence gene expression in vivo. INTRODUCTIONStreptococcus pneumoniae (the pneumococcus) is a globally significant pathogen, responsible for invasive diseases such as pneumonia, bacteraemia and meningitis . The pneumococcus asymptomatically colonizes the nasopharynx, and such carriage is considered essential for subsequent development of disease in susceptible individuals (particularly infants, the elderly, and the immunocompromised). Disease commonly occurs following the aspiration of bacteria from the nasopharynx into the lungs, followed by colonization of the pulmonary epithelium and subsequent development of pneumonia. From this niche, the pneumococcus can invade the bloodstream and cause sepsis. Alternatively, bacteraemia can occur, following direct translocation from the nasopharyngeal epithelium into underlying tissues. The gene regulatory mechanisms involved in transition between, and survival in, these distinct host niches are poorly understood. This has primarily been due to technical difficulties in harvesting sufficient quantities of pneumococci from an animal model to perform accurate and quantitative RNA assays, particularly from niches such as the nasopharynx, in which bacteria exist asymptomatically and in low numbers.Several studies have been conducted in recent years comparing in vivo and in vitro pneumococcal gene expression. Orihuela et al. (2000) used Northern blotting to assess virulence gene mRNA levels in type 3 pneumococci grown in sealed dialysis bags implanted in the murine peritoneal cavity. In another study, differences in gene expression between virulent type 2 pneumococci harvested from the blood of mice infected intraperitoneally and those grown in serum broth were examined using semi-quantitative RT-PCR (Ogunniyi et al., 2002). More recently, in vivo studies have used microarray technology to quantitate S. pneumoniae transcript abundance in the blood of infected mice and the cerebrospinal fluid of infected rabbits (Orihuela et al., 2004b).The present work is the first to evaluate in vivo changes in pneumococcal gene expression during the natural progression of disease from colonization of the nasopharynx to invasion of the lungs...

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“…Recruitment of factor H by Hic has been shown to efficiently prevent activation of C3b and complement-mediated opsonophagocytosis of pneumococci (Jarva et al, 2004). The improved survival of pneumococci expressing PspC or Hic in a systemic mouse infection model provides further evidence for the versatility and importance of PspC in different host niches (Iannelli et al, 2004;Quin et al, 2005).…”

Section: Biological Activities Of Unusually Cell-wallanchored Cholinementioning

confidence: 99%

Versatility of pneumococcal surface proteins

2006

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Surface-exposed proteins are key players during the infectious process of pathogenic bacteria. The cell surface of the Gram-positive human pathogen Streptococcus pneumoniae is decorated not only by typical Gram-positive surface proteins, but also by a family of proteins that recognizes the phosphorylcholine of the lipoteichoic and teichoic acids, namely the choline-binding proteins, and by non-classical surface proteins that lack a leader peptide and membrane-anchor motif. A comprehensive understanding of how microbial proteins subvert host immunity or host protein functions is a prerequisite for the development of novel therapeutic strategies to combat pneumococcal infections. This article reviews recent progress in the investigation of the versatility and sophistication of the virulence functions of surface-exposed pneumococcal proteins.

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Pneumococcal Surface Protein C Contributes to Sepsis Caused byStreptococcus pneumoniaein Mice

Cited by 72 publications

References 21 publications

The Host Immune Regulator Factor H Interacts via Two Contact Sites with the PspC Protein of Streptococcus pneumoniae and Mediates Adhesion to Host Epithelial Cells

The Host Immune Regulator Factor H Interacts via Two Contact Sites with the PspC Protein of Streptococcus pneumoniae and Mediates Adhesion to Host Epithelial Cells

Differential expression of key pneumococcal virulence genes in vivo

Versatility of pneumococcal surface proteins

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