scholarly journals The Contribution of PspC to Pneumococcal Virulence Varies between Strains and Is Accomplished by Both Complement Evasion and Complement-Independent Mechanisms

2006 ◽  
Vol 74 (9) ◽  
pp. 5319-5324 ◽  
Author(s):  
Alison R. Kerr ◽  
Gavin K. Paterson ◽  
Jackie McCluskey ◽  
Francesco Iannelli ◽  
Marco R. Oggioni ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Pneumococcal Pneumonia ◽  
Surface Protein ◽  
Murine Models ◽  
Wild Type ◽  
Survival Times ◽  
Pneumococcal Strain ◽  
Wild Type Parent

ABSTRACTPneumococcal surface protein C (PspC) is a virulence factor ofStreptococcus pneumoniaepreviously shown to play a role in bacterial adherence, invasion, and evasion of complement. We investigated the role of this protein in our murine models of pneumococcal pneumonia with different pneumococcal strains. The deletion ofpspCin strains of serotypes 2, 3, and 19F did not significantly alter host survival times in the pneumonia model. In contrast,pspCdeletion significantly reduced the virulence of the serotype 4 strain, TIGR4, in both the pneumonia and bacteremia models. Therefore,pspCis a systemic and pulmonary virulence determinant forS. pneumoniae, but its effects are influenced by the pneumococcal strain. Finally, pneumonia infection of complement-deficient (C3−/−) mice enhancedpspCvirulence, illustrating that PspC-mediated complement evasion contributes to virulence. However, other functions of PspC also contribute to virulence, as demonstrated by the finding that thepspC-deficient TIGR4 mutant was still attenuated relative to the wild-type parent, even in the absence of C3.

scholarly journals Pneumococcal Surface Protein C Contributes to Sepsis Caused by Streptococcus pneumoniae in Mice

2004 ◽  
Vol 72 (5) ◽  
pp. 3077-3080 ◽  
Author(s):  
Francesco Iannelli ◽  
Damiana Chiavolini ◽  
Susanna Ricci ◽  
Marco Rinaldo Oggioni ◽  
Gianni Pozzi
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Lethal Dose ◽  
Surface Protein ◽  
Infection Model ◽  
Wild Type ◽  
Mutant Strains ◽  
Type 3

ABSTRACT The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis by Streptococcus pneumoniae was investigated in a murine infection model. The pspC gene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice. The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type. Our findings indicate that PspC affords a decisive contribution to sepsis development.

scholarly journals Role of Pneumococcal Surface Protein C in Nasopharyngeal Carriage and Pneumonia and Its Ability To Elicit Protection against Carriage of Streptococcus pneumoniae

2002 ◽  
Vol 70 (5) ◽  
pp. 2526-2534 ◽  
Author(s):  
Priya Balachandran ◽  
Alexis Brooks-Walter ◽  
Anni Virolainen-Julkunen ◽  
Susan K. Hollingshead ◽  
David E. Briles
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Surface Protein ◽  
Wild Type ◽  
Nasal Tissue ◽  
Cholera Toxin Subunit B ◽  
Colonization Model ◽  
Subunit B

ABSTRACT Previous studies suggested that PspC is important in adherence and colonization within the nasopharynx. In this study, we conducted mutational studies to further identify the role PspC plays in the pathogenesis of pneumococci. pspC and/or pspA was insertionally inactivated in a serotype 2 Streptococcus pneumoniae strain and in a serotype 19 S. pneumoniae strain. In the mouse colonization model, pneumococcal strains with mutations in pspC were significantly attenuated in their abilities to colonize. In a mouse pneumonia model, strains with mutations in pspC were unable to infect or multiply within the lung. Using reverse transcriptase PCR we were able to demonstrate that pspC is actively transcribed in vivo, when the bacteria are growing in the nasal cavity and in the lungs. In the bacteremia model, a strain mutated for pspC alone behaved like the wild type, but the absence of both pspC and pspA caused accelerated clearance of the bacteria. Intranasal immunization with PspC with cholera toxin subunit B as an adjuvant protected against intranasal challenge. Evidence was also obtained that revertants that spontaneously acquired PspC expression could multiply and colonize the nasal tissue. This latter finding strongly indicates that pneumococci are actively metabolizing and growing while in the nasopharynx.

scholarly journals Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

2008 ◽  
Vol 76 (6) ◽  
pp. 2767-2776 ◽  
Author(s):  
David T. Glover ◽  
Susan K. Hollingshead ◽  
David E. Briles
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Surface Protein ◽  
Murine Models ◽  
Wild Type ◽  
Survival Times ◽  
High Manganese ◽  
Subcutaneous Immunization ◽  
Fatal Sepsis ◽  
Manganese Concentrations

ABSTRACTPrevious studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence ofStreptococcus pneumoniae, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewerS. pneumoniaecells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4- to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.

Role of interleukin-18 in experimental infections with Streptococcus pneumoniae

2005 ◽  
Vol 54 (4) ◽  
pp. 323-326 ◽  
Author(s):  
G K Paterson ◽  
C E Blue ◽  
T J Mitchell
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Pneumonia ◽  
Infection Type ◽  
Bacterial Species ◽  
Murine Models ◽  
Positive Bacterium ◽  
Nasopharyngeal Colonization ◽  
Complex Influence ◽  
Multifunctional Cytokine

IL-18, a multifunctional cytokine, has been shown to be involved in the immune response to numerous pathogens including several bacterial species. To study its role in infection by the Gram-positive bacterium Streptococcus pneumoniae, wild-type and IL-18 knockout BALB/c mice were compared in murine models of pneumococcal pneumonia, bacteraemia and nasopharyngeal colonization. The influence of IL-18 varied with the infection type, whereby it contributed to increased bacterial loads in pneumonia, reduced levels of colonization and had no effect on levels of bacteraemia following intravenous challenge. Likewise, the influence of IL-18 on pneumonia varied between two infecting pneumococcal strains. Comparison of these results with previous data also suggested that the influence of IL-18 in pneumococcal pneumonia differs with the mouse strain genetic background. Overall, these results demonstrate the complex influence of IL-18 in the response to the pneumococcus.

scholarly journals A genetic interaction screen in Streptococcus pneumoniae identifies functionally redundant vaccine candidate proteins CbpC and CbpJ

2021 ◽  
Author(s):  
Lisa M Russo ◽  
Allison J Matthews ◽  
revati masilamani ◽  
David W Lazinski ◽  
Andrew Camilli
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Pneumonia ◽  
Immune Escape ◽  
Genetic Interaction ◽  
Surface Protein ◽  
Invasive Disease ◽  
Surface Proteins ◽  
Protein Vaccine ◽  
Survival Times ◽  
Genetic Robustness

Streptococcus pneumoniae is a Gram-positive bacterium that asymptomatically colonizes the nasopharynx and can disseminate to sterile sites resulting in pneumococcal diseases such as pneumonia, otitis media, bacteremia, and meningitis. Due to increased incidence of invasive disease caused by serotypes that are not included in available polysaccharide vaccines, there is a need for a broadly protective protein vaccine to complement the polysaccharide based vaccines. To limit immune escape such a vaccine would ideally target proteins that are essential for virulence. However, the genetic robustness of S. pneumoniae results in few surface exposed proteins being essential for virulence. Here we carried out a genetic interaction screen to identify functionally redundant surface protein pairs that could be used as bivalent protein vaccines, based on the observation that together, these protein pairs are essential for virulence. We identified four pairs of functionally redundant surface proteins that displayed a significant competitive disadvantage during murine pneumococcal pneumonia. Immunization with the most attenuated pair, CbpC and CbpJ, resulted in production of high titers of specific antibodies and a modest increased median survival times of mice challenged with pneumococcal pneumonia. This study demonstrates a method to identify essential pairs of surface-associated virulence proteins that could be widely applied to many bacterial pathogens.

scholarly journals The Ami-AliA/AliB Permease of Streptococcus pneumoniae Is Involved in Nasopharyngeal Colonization but Not in Invasive Disease

2004 ◽  
Vol 72 (7) ◽  
pp. 3902-3906 ◽  
Author(s):  
A. R. Kerr ◽  
P. V. Adrian ◽  
S. Estevão ◽  
R. de Groot ◽  
G. Alloing ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Disease ◽  
Wild Type ◽  
Survival Times ◽  
Triple Mutant ◽  
Nasopharyngeal Colonization ◽  
Atp Binding Cassette Transporter ◽  
Pneumococcal Colonization ◽  
Oligopeptide Permease

ABSTRACT The Ami-AliA/AliB oligopeptide permease is an ATP-binding cassette transporter which is found in Streptococcus pneumoniae and which is involved in nutrient uptake. We investigated the role of the three paralogous oligopeptide-binding lipoproteins AmiA, AliA, and AliB by using murine models of pneumococcal colonization and invasive disease. A series of mutants lacking aliA, aliB, and amiA either alone or in combination as double or triple mutations were used. Inoculation of the nasopharynx with a mixture of the obl (oligopeptide-binding lipoprotein-negative) triple-mutant and wild-type (D39) bacteria resulted in significantly smaller numbers of obl bacteria colonizing the nasopharynx. The use of a mixture of individual mutants and wild-type pneumococci revealed that AmiA, AliA, and AliB were all required for successful colonization of the nasopharynx. The obl mutant was more attenuated than the aliB mutant but not the aliA or amiA mutant. Therefore, there is some redundancy in the Ami-AliA/AliB complex in terms of nasopharyngeal colonization, with AliA and AmiA being able to compensate for the removal of AliB. Animals with invasive disease caused by these mutants had survival times, bacterial loads, and inflammatory cytokine production levels similar to those of animals infected with wild-type pneumococci. Our results show that although the Ami-AliA/AliB complex is not required for virulence during pneumococcal pneumonia, it does play a role in colonization of the nasopharynx.

scholarly journals Monocyte Chemoattractant Protein 1 Does Not Contribute to Protective Immunity against Pneumococcal Pneumonia

2006 ◽  
Vol 74 (12) ◽  
pp. 7021-7023 ◽  
Author(s):  
Mark C. Dessing ◽  
Alex F. de Vos ◽  
Sandrine Florquin ◽  
Tom van der Poll
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protective Immunity ◽  
Pneumococcal Pneumonia ◽  
Inflammatory Responses ◽  
Strongly Correlated ◽  
Wild Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

ABSTRACT To determine the role of monocyte chemoattractant protein 1 (MCP-1) during pneumococcal pneumonia, MCP-1 knockout and wild-type mice were infected with Streptococcus pneumoniae. Pulmonary MCP-1 levels were strongly correlated to bacterial loads in wild-type mice. However, MCP-1 knockout and wild-type mice were indistinguishable with respect to bacterial growth, inflammatory responses, and lethality.

The endothelial protein C receptor impairs the antibacterial response in murine pneumococcal pneumonia and sepsis

2014 ◽  
Vol 111 (05) ◽  
pp. 970-980 ◽  
Author(s):  
J. Daan de Boer ◽  
Liesbeth M. Kager ◽  
Joris J. T. H. Roelofs ◽  
Joost C. M. Meijers ◽  
Charles T. Esmon ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Bacterial Growth ◽  
Protein C ◽  
Pneumococcal Pneumonia ◽  
Wild Type ◽  
Endothelial Protein C Receptor ◽  
Pulmonary Endothelium ◽  
Pneumococcal Sepsis ◽  
Bacterial Outgrowth

SummaryPneumococcal pneumonia is a frequent cause of gram-positive sepsis and has a high mortality. The endothelial protein C receptor (EPCR) has been implicated in both the activation of protein C (PC) and the anti-inflammatory actions of activated (A)PC. The aim of this study was to determine the role of the EPCR in murine pneumococcal pneumonia and sepsis. Wild-type (WT), EPCR knockout (KO) and Tie2-EPCR mice, which overexpress EPCR on the endothelium, were infected intranasally (pneumonia) or intravenously (sepsis) with viable Streptococcus pneumoniae and euthanised at 24 or 48 hours after initiation of the infection for analyses. Pneumonia did not alter constitutive EPCR expression on pulmonary endothelium but was associated with an influx of EPCR positive neutrophils into lung tissue. In pneumococcal pneumonia EPCR KO mice demonstrated diminished bacterial growth in the lungs and dissemination to spleen and liver, reduced neutrophil recruitment to the lungs and a mitigated inflammatory response. Moreover, EPCR KO mice displayed enhanced activation of coagulation in the early phase of disease. Correspondingly, in pneumococcal sepsis EPCR KO mice showed reduced bacterial growth in lung and liver and attenuated cytokine release. Conversely, EPCR-overexpressing mice displayed higher bacterial outgrowth in lung, blood, spleen and liver in pneumococcal sepsis. In conclusion, EPCR impairs antibacterial defense in both pneumococcal pneumonia and sepsis, which is associated with an enhanced pro-inflammatory response.

scholarly journals Role of FAD-I in Fusobacterial Interspecies Interaction and Biofilm Formation

2020 ◽  
Vol 8 (1) ◽  
pp. 70 ◽  
Author(s):  
Bhumika Shokeen ◽  
Jane Park ◽  
Emily Duong ◽  
Sonam Rambhia ◽  
Manash Paul ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Fusobacterium Nucleatum ◽  
Interspecies Interaction ◽  
Wild Type ◽  
Oral Epithelial Cells ◽  
Small Proteins ◽  
Mutant Strains ◽  
Oral Epithelial ◽  
Wild Type Parent

RadD, a major adhesin of oral fusobacteria, is part of a four-gene operon encoding the small lipoprotein FAD-I and two currently uncharacterized small proteins encoded by the rapA and rapB genes. Previously, we described a role for FAD-I in the induction of human B-defensin 2 (hBD2) upon contact with oral epithelial cells. Here, we investigated potential roles for fad-I, rapA, and rapB in interspecies interaction and biofilm formation. Gene inactivation mutants were generated for each of these genes in the nucleatum and polymorphum subspecies of Fusobacterium nucleatum and characterized for their adherence to partner species, biofilm formation, and operon transcription. Binding to Streptococcus gordonii was increased in all mutant strains with Δfad-I having the most significant effect. This increased adherence was directly proportional to elevated radD transcript levels and resulted in significantly different architecture and height of the biofilms formed by Δfad-I and S. gordonii compared to the wild-type parent. In conclusion, FAD-I is important for fusobacterial interspecies interaction as its lack leads to increased production of the RadD adhesin suggesting a role of FAD-I in its regulation. This regulatory effect does not require the presence of functional RadD.

scholarly journals Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection

2019 ◽  
Vol 220 (5) ◽  
pp. 902-912 ◽  
Author(s):  
Ganesh Ambigapathy ◽  
Taylor Schmit ◽  
Ram Kumar Mathur ◽  
Suba Nookala ◽  
Saad Bahri ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Puerto Rico ◽  
Streptococcus Pneumoniae ◽  
Influenza A ◽  
Invasive Disease ◽  
Wild Type ◽  
Interleukin 17A ◽  
Influenza A H1n1 ◽  
Virus Influenza

AbstractBackgroundWe sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8).MethodWild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoRγt−/− and RAG1−/− mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1−/−).ResultsRAG1−/− mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoRγt−/− mice also had reduced clearance. S. pneumoniae–PR8 coinfection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced S. pneumoniae invasive disease. RoRγt−/− mice also had reduced S. pneumoniae disease in a coinfection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced S. pneumoniae invasion in RAG1−/− mice.ConclusionOur data show that although IL-17A reduces S. pneumoniae colonization, coinfection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and S. pneumoniae disease in the nasopharynx.

Sign in / Sign up

Export Citation Format

Share Document