Disease relevance of SP_0117

• PspA is a cell surface protein of Streptococcus pneumoniae that is present on a number of clinical isolates as well as the nonencapsulated laboratory strain Rx1 [1].
• Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A [2].
• Pneumococcal surface protein A (PspA) elicits protection in mice against fatal bacteremia and sepsis caused by genetically diverse pneumococci and protects against carriage and lung infection [3].
• The abilities of the mutant deficient in PspA to colonize the nasopharynx and to cause lung infection and bacteremia were significantly reduced [4].
• Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media [5].

High impact information on SP_0117

• Pneumococcal surface protein A (PspA), a cell-surface protein present on all strains of pneumococci, has been shown to elicit protective antibody responses in mice in the absence of capsular polysaccharide [2].
• A gene segment encoding the nonrepetitive variable NH2-terminal portion of PspA has been cloned into three distinct recombinant Bacille Calmette-Guérin (rBCG) vectors, allowing for expression of PspA as a cytoplasmic or secreted protein, or a chimeric exported membrane-associated lipoprotein [2].
• Pneumococci carrying defined mutations in the genes encoding any one of at least three pneumococcal proteins (the toxin pneumolysin, the major pneumococcal autolysin, and pneumococcal surface protein A) have significantly reduced virulence [6].
• This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains [7].
• We demonstrate that the IgG (but not IgM), anti-PPS14, and anti-PspA responses to Pn14 are CD4+ T cell dependent and TCR specific [8].

Chemical compound and disease context of SP_0117

• We used heat-killed, intact Streptococcus pneumoniae, capsular type 14 (Pn14), to evaluate the IgM and IgG responses specific for the capsular polysaccharide (PPS14), the phosphorylcholine determinant of the cell wall C-polysaccharide, and the cell wall protein, pneumococcal surface protein A (PspA) [8].
• We previously reported that the in vivo Ig responses to Streptococcus pneumoniae (strain R36A), specific for pneumococcal surface protein A (PspA) and for the phosphorylcholine (PC) determinant of C-polysaccharide, were both dependent on TCR-alphabeta(+) T cells and B7-dependent costimulation, although only PspA-specific memory was generated [9].
• Surface binding of lactoferrin and interference with C3 deposition by the two types of PspA proteins were determined by flow cytometry, and virulence was assessed in a mouse bacteremia model [10].
• The immune response to pneumococcal capsular polysaccharides (CPSs) and to the pneumococcal surface proteins cell wall-associated serine proteinase A (PrtA), pneumococcal surface protein A (PspA), and Streptococcus pneumoniae pullulanase A was evaluated in 45 patients with invasive pneumococcal disease compared with healthy adults [11].
• In contrast to that of surface proteins from other gram-positive bacteria, PspA anchoring required choline-mediated interactions between the membrane-associated lipoteichoic acid and the C-terminal repeat region of PspA [12].

Biological context of SP_0117

• In our present report we have produced insertional inactivation mutants that lack PspA and have used these mutants to demonstrate that PspA can play a role in pneumococcal virulence and that anti-PspA immunity can lead to protection against pneumococcal infection [1].
• 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 [13].
• A nontoxic adjuvant for mucosal immunity to pneumococcal surface protein A [14].
• PspA has recently been implicated in anti-complementary function as it reduces complement-mediated clearance and phagocytosis of pneumococci [15].
• Nevertheless, in contrast to the anti-PspA response, the IgG anti-PPS14 response shows no apparent memory, an accelerated kinetics of primary Ig induction, and a more rapid delivery of CD4+ T cell help [8].

Anatomical context of SP_0117

• Immunization with PspA and mCT elicited higher levels of PspA-specific IgG and IgA Abs in serum and of IgG and IgA anti-PspA Ab-forming cells in spleens, cervical lymph nodes (CLN), and lung tissue when compared to nonimmunized mice [14].
• After oral immunization, the recombinant Salmonella-PspA vaccine strain colonized the Peyer's patches, spleens, and livers of BALB/cByJ and CBA/N mice and stimulated humoral and mucosal antibody responses [16].
• Thus, the N termini of CbpA and PspA exert differential effects on CXC chemokine induction in epithelial cells infected with S. pneumoniae [17].
• Mice on the zinc-deficient diet showed substantially reduced immune responses to PspA, more extensive pneumococcal colonization in the nasal mucosa, more severe infections, and an increased risk of death [18].
• Taken together, these findings suggest that PsaA- and PspA-specific mucosal responses as well as systemic humoral and T helper cell cytokine responses are predominantly yet differentially induced during pneumococcal carriage [19].

Associations of SP_0117 with chemical compounds

• In contrast, very little C3 was deposited on the PspA+ strain [20].
• In contrast, in C5-deficient mice as in wild-type mice, PspA-deficient pneumococci were avirulent [21].
• Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs an asd deletion in the host chromosome to impose an obligate requirement for diaminopimelic acid [16].
• Protein types P23 differed from P0 by a single epitope on pneumococcal surface protein A. These results suggest that the Canadian P23 and P0 capsular group 9 isolates are likely subclones of a primordial 9L RPR strain [22].
• During growth in the presence of choline, which was incorporated as phosphocholine into LTA and TA, the mutant cells separated normally, did not release PspA, and became penicillin sensitive [23].

Other interactions of SP_0117

• Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae [24].

Analytical, diagnostic and therapeutic context of SP_0117

• All rBCG-PspA strains elicited comparable anti-PspA ELISA titers, ranging from 10(4) to 10(5) (reciprocal titers) in both BALB/c and C3H/HeJ mice [2].
• These results show that intranasal administration of PspA together with mCT S61F is an effective mucosal vaccine against pneumococcal infection and induces CD4+ Th2-type cells, which provide help for both mucosal and systemic Ab responses [14].
• In addition, i.n. vaccination with PspA and IL-12 provided increased protection against nasopharyngeal carriage [25].
• The presence of genes encoding PsaA, PpmA, and PspA in 11 clinical isolates was examined by PCR, and the expression of these proteins by each strain was examined by Western blotting with antisera raised to the respective recombinant proteins [26].
• We used flow cytometry to demonstrate that PspA was readily detectable on the surface of the pneumococcal strains analyzed, whereas PsaA and PpmA were not [26].

References