scholarly journals Immunization with Components of Two Iron Uptake ABC Transporters Protects Mice against Systemic Streptococcus pneumoniae Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6702-6706 ◽  
Author(s):  
Jeremy S. Brown ◽  
A. David Ogunniyi ◽  
Matthew C. Woodrow ◽  
David W. Holden ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporters ◽  
Iron Uptake ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Systemic Infection ◽  
Antibody Responses ◽  
Protein Vaccine ◽  
Protein Antigens ◽  
Bacterial Cell Membrane

ABSTRACT There has been considerable recent research into protein basedStreptococcus pneumoniae vaccines as alternatives to the existing capsular antigen vaccines. PiuA and PiaA (formerly Pit1A and Pit2A) are recently identified lipoprotein components of S. pneumoniae iron uptake ABC transporters which are required for full virulence and are likely to be expressed on the surface of the bacterial cell membrane. We investigated the efficacy of recombinant PiuA and PiaA proteins at eliciting protective immunity in mice against systemic infection with S. pneumoniae. Both recombinant PiuA and PiaA generated antibody responses that cross-reacted with each other but not with pneumolysin and reacted with identical proteins from nine different S. pneumoniae serotypes. Mice immunized with recombinant PiuA and PiaA were protected against systemic challenge to a degree similar to those immunized with an existing protein vaccine candidate, PdB (a genetically modified pneumolysin toxoid). Immunization with a combination of both PiuA and PiaA resulted in additive protection and was highly protective against systemic infection with S. pneumoniae. PiuA and PiaA are therefore promising additional candidates for a novel S. pneumoniae vaccine using protein antigens.

scholarly journals Antibodies to the Iron Uptake ABC Transporter Lipoproteins PiaA and PiuA Promote Opsonophagocytosis of Streptococcus pneumoniae

2005 ◽  
Vol 73 (10) ◽  
pp. 6852-6859 ◽  
Author(s):  
Maha Jomaa ◽  
Jose Yuste ◽  
James C. Paton ◽  
Christopher Jones ◽  
Gordon Dougan ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporters ◽  
Iron Uptake ◽  
Iron Transport ◽  
Antibody Responses ◽  
Igg Subclass ◽  
Specific Enzyme ◽  
Low Levels ◽  
Passive Vaccination ◽  
Neutrophil Cell

ABSTRACT PiaA and PiuA are the lipoprotein components of the Pia and Piu Streptococcus pneumoniae iron uptake ABC transporters and are required for full virulence in mouse models of infection. Active or passive vaccination with recombinant PiuA and PiaA protects mice against invasive S. pneumoniae disease. In this study we have analyzed the antibody responses and mechanism of protection induced by PiuA and PiaA in more detail. For both proteins, two booster vaccinations induced stronger antibody responses in mice than a single or no booster vaccinations, and 5 μg of protein induced similar levels of antibody responses as 20 μg. Immunoglobulin G (IgG) subclass-specific enzyme-linked immunosorbent assays demonstrated that the antibody response to PiuA and PiaA was predominantly IgG1, with induction of only low levels of IgG2a. Anti-PiaA and anti-PiuA polyclonal rabbit antibodies bound to the surface of live S. pneumoniae when assessed by flow cytometry but did not inhibit growth of S. pneumoniae in cation-depleted medium or bacterial susceptibility to the iron-dependent antibiotic streptonigrin. However, anti-PiaA and anti-PiuA did increase complement-independent and -dependent opsonophagocytosis of different serotypes of S. pneumoniae by the human neutrophil cell line HL60. Hence, vaccination with PiaA and PiuA protects against S. pneumoniae infection by inducing antibodies that promote bacterial opsonophagocytosis rather than inhibiting iron transport.

scholarly journals Characterization of Pit, a Streptococcus pneumoniae Iron Uptake ABC Transporter

2002 ◽  
Vol 70 (8) ◽  
pp. 4389-4398 ◽  
Author(s):  
Jeremy S. Brown ◽  
Sarah M. Gilliland ◽  
Javier Ruiz-Albert ◽  
David W. Holden
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporter ◽  
Iron Uptake ◽  
Systemic Infection ◽  
Iron Chelator ◽  
Iron Deficient ◽  
Deficient Medium ◽  
Mutant Strains

ABSTRACT Bacteria frequently have multiple mechanisms for acquiring iron, an essential micronutrient, from the environment. We have identified a four-gene Streptococcus pneumoniae operon, named pit, encoding proteins with similarity to components of a putative Brachyspira hyodysenteriae iron uptake ABC transporter, Bit. An S. pneumoniae strain containing a defined mutation in pit has impaired growth in medium containing the iron chelator ethylenediamine di-o-hydroxyphenylacetic acid, reduced sensitivity to the iron-dependent antibiotic streptonigrin, and impaired virulence in a mouse model of S. pneumoniae systemic infection. Furthermore, addition of a mutation in pit to a strain containing mutations in the two previously described S. pneumoniae iron uptake ABC transporters, piu and pia, resulted in a strain with impaired growth in two types of iron-deficient medium, a high degree of resistance to streptonigrin, and a reduced rate of iron uptake. Comparison of the susceptibilities to streptonigrin of the individual pit, piu, and pia mutant strains and comparison of the growth in iron-deficient medium and virulence of single and double mutant strains suggest that pia is the dominant iron transporter during in vitro and in vivo growth.

scholarly journals Infection with Conditionally Virulent Streptococcus pneumoniae ΔpabStrains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

2011 ◽  
Vol 79 (12) ◽  
pp. 4965-4976 ◽  
Author(s):  
Suneeta Chimalapati ◽  
Jonathan Cohen ◽  
Emilie Camberlein ◽  
Claire Durmort ◽  
Helen Baxendale ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Bacterial Pathogen ◽  
Systemic Infection ◽  
Complete Medium ◽  
Protein Antigens ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Immunological Responses ◽  
Heterologous Challenge

ABSTRACTAvirulent strains of a bacterial pathogen could be useful tools for investigating immunological responses to infection and potentially effective vaccines. We have therefore constructed an auxotrophic TIGR4 Δpabstrain ofStreptococcus pneumoniaeby deleting thepabBgene Sp_0665. The TIGR4 Δpabstrain grew well in complete medium but was unable to grow in serum unless it was supplemented withpara-aminobenzoic acid (PABA). The TIGR4 Δpabstrain was markedly attenuated in virulence in mouse models ofS. pneumoniaenasopharyngeal colonization, pneumonia, and sepsis. Supplementing mouse drinking water with PABA largely restored the virulence of TIGR4 Δpab. An additional Δpabstrain constructed in the D39 capsular serotype 2 background was also avirulent in a sepsis model. Systemic inoculation of mice with TIGR4 Δpabinduced antibody responses toS. pneumoniaeprotein antigens, including PpmA, PsaA, pneumolysin, and CbpD, but not capsular polysaccharide. Flow cytometry demonstrated that IgG in sera from TIGR4 Δpab-vaccinated mice bound to the surface of TIGR4 and D39 bacteria but not to a capsular serotype 3 strain, strain 0100993. Mice vaccinated with the TIGR4 Δpabor D39 Δpabstrain by intraperitoneal inoculation were protected from developing septicemia when challenged with the homologousS. pneumoniaestrain. Vaccination with the TIGR4 Δpabstrain provided only weak or no protection against heterologous challenge with the D39 or 0100993 strain but did strongly protect against a TIGR4 capsular-switch strain expressing a serotype 2 capsule. The failure of cross-protection after systemic vaccination with Δpabbacteria suggests that parenteral administration of a live attenuated vaccine is not an attractive approach for preventingS. pneumoniaeinfection.

scholarly journals Immunization with Components of Two Iron Uptake ABC Transporters Protects Mice against Systemic Streptococcus pneumoniae Infection

2004 ◽  
Vol 72 (11) ◽  
pp. 6755-6755
Author(s):  
Jeremy S. Brown ◽  
A. David Ogunniyi ◽  
Matthew C. Woodrow ◽  
David W. Holden ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporters ◽  
Iron Uptake

scholarly journals Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L

2000 ◽  
Vol 68 (2) ◽  
pp. 511-517 ◽  
Author(s):  
Young-il Hwang ◽  
Moon H. Nahm ◽  
David E. Briles ◽  
David Thomas ◽  
Jeffrey M. Purkerson
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Pneumococcal Infection ◽  
Systemic Infection ◽  
Humoral Response ◽  
Nasal Carriage ◽  
The Elderly ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Cell Wall Polysaccharides

ABSTRACT Streptococcus pneumoniae is a significant pathogen of young children and the elderly. Systemic infection by pneumococci is a complex process involving several bacterial and host factors. We have investigated the role of CD40L in host defense against pneumococcal infection. Treatment of mice with MR-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides. MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent. Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci. Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.

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