Disease relevance of pspA

• Regulation of the pspA virulence factor and essential pcsB murein biosynthetic genes by the phosphorylated VicR (YycF) response regulator in Streptococcus pneumoniae [1].
• 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 [2].

High impact information on pspA

• Gene expression in blood was characterized by increased expression of pneumolysin, pspA and hrcA, while pneumococci in tissue infection showed increased expression of neuraminidases, metalloproteinases, oxidative stress and competence genes [3].
• 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 [2].
• Mutagenesis of either the ply, lytA, or pspA gene in S. pneumoniae D39 significantly reduced virulence, relative to that of the wild-type strain, indicating that the respective gene products contribute to pathogenesis [4].
• However, significant additive attenuation in virulence was observed for the strains with ply-hyl, ply-pspA, and ply-cbpA double mutations [4].
• The extensive recombination which generated the mosaic pattern seen in the pspA locus suggests that natural selection has operated in the history of this gene locus and underscores the likelihood that PspA may be important in the interaction between the pneumococcus and its human host [5].

Biological context of pspA

• To date, a published DNA sequence for pspA is available only for S. pneumoniae Rx1, a laboratory strain [6].
• The gene is paralogous to the pspA gene in S. pneumoniae and was thus called pspC (A. Brooks-Walter, R. C. Tart, D. E. Briles, and S. K. Hollingshead, Abstracts of the 97th General Meeting of the American Society for Microbiology 1997) [7].
• All RPR type 9L strains demonstrated an identical RFLP when probed with IS1167, and 12 of 14 RPR strains had the same RFLP when examined with pspA [8].
• Additionally, nearly all pneumococcal strains contain at least one other locus with sequence homology to pspA [9].
• Thus, the 3'-half of pspA appears to contain more highly conserved sequences than the 5'-half of pspA and shares homology with several additional sequences, suggesting that the pneumococcus might make several proteins that interact with the surface by the same mechanism as PspA [10].

Anatomical context of pspA

• When pspA was inactivated in three virulent, encapsulated strains of pneumococci, all three strains showed a reduction in virulence and two became totally avirulent: the 50% lethal dose was less than 10 colony-forming units (cfu) for the parents and greater than 5 x 10(4) cfu for the PspA- mutants [11].

Associations of pspA with chemical compounds

• Sequences encoding the leader peptide, the proline-rich region, and the repeat region are highly conserved among pspA and pspA-like sequences [9].
• The remaining genes included several virulence factors, such as capsular genes, iga, lytB, nanB, pspA, choline-binding proteins, and functions related to DNA acquisition, such as restriction-modification systems and comDE [12].

Other interactions of pspA

• DNase I footprinting of VicR and VicR-P bound to regions upstream of pcsB, pspA, spr0096, and spr1875 showed protection of extended regions containing a degenerate sequence related to a previously proposed consensus [1].
• To test this hypothesis, restriction fragment length polymorphisms (RFLPs) were examined using DNA probes for pspA and a newly recognized pneumococcal genetic element, IS1167 [8].
• Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types [13].
• The expression of ply was upregulated threefold at 12 h, and 10-fold at 24 h post-infection; the expression of pspA and psaA was upregulated threefold and fivefold, respectively, at 12 h post-infection [14].
• Interestingly, the expression of pspA was 36-fold higher at 24 h post-infection whereas the expression of cps2A was upregulated approximately fourfold at 12 and 24 h post-infection [14].

Analytical, diagnostic and therapeutic context of pspA

• Twenty-four diverse alleles of the pspA gene were sequenced to investigate the genetic basis for serologic diversity and to evaluate the potential of diversity to have an impact on PspA's use in human vaccination [5].
• Distinct, conserved pspA sequence types were found for the majority of strains within seven of the eight U.S. clonal types assessed, while one pulsed-field gel electrophoresis type was represented by isolates of three distinct PspA clades [15].
• In order to investigate the properties of this protein, several internal fragments of the pspA gene were amplified from S. pneumoniae strain Rxl using the polymerase chain reaction (PCR) [16].

References