Allelic variation in the highly polymorphic locus pspC of Streptococcus pneumoniae
Introduction
Surface proteins of Streptococcus pneumoniae (pneumococcus) have been investigated for their role in pneumococcal pathogenicity and as candidate antigens for protein-based vaccines. The most extensively studied molecule is pneumococcal surface protein A (PspA), which was shown to be essential for virulence and to elicit protection against pneumococcal infection (McDaniel et al., 1987, Briles et al., 1998, Briles et al., 2000, Ogunniyi et al., 2000). While typical surface proteins of gram-positive bacteria are covalently linked to the cell wall via the LPXTG motif at their C-terminal end (Navarre and Schneewind, 1999), PspA was found to be attached by a novel mechanism by which its C-terminal repeat region binds to the choline residues of the lipoteichoic acid of S. pneumoniae (Yother and White, 1994). By searching the pneumococcal genome data (Tettelin et al., 2001, Dopazo et al., 2001, Hoskins et al., 2001, Oggioni and Pozzi, 2001) it is possible to identify a variety of C-terminally anchored surface proteins, which contain the LPXTG motif or the choline-binding domain.
Different biological functions have been associated with pneumococcal surface protein C (PspC), and different allelic forms of PspC have been referred to by different names, including choline-binding protein A (CbpA) (Rosenow et al., 1997), S. pneumoniae secretory IgA binding protein (SpsA) (Hammerschmidt et al., 1997), C3-binding protein A (PbcA) (Cheng et al., 2000), and factor H-binding inhibitor of complement (Hic) (Janulczyk et al., 2000). PspC plays an important role in pneumococcal pathogenesis by functioning as an adhesin (Rosenow et al., 1997), by promoting invasion of epithelial cells (Zhang et al., 2000), and by binding soluble host factors such as the IgA secretory fragment, C3 and complement factor H (Hammerschmidt et al., 1997, Cheng et al., 2000, Janulczyk et al., 2000, Dave et al., 2001). Used as an immunogen in the mouse model, PspC proved to be a good candidate for anti-pneumococcal vaccines (Brooks-Walter et al., 1999, Briles et al., 2000).
Given this multiplicity of phenotypes, it is important to investigate the variability of the pspC locus among different isolates, to gain a better understanding of PspC as a virulence factor and to facilitate design of PspC-based vaccines. In this work we characterized the pspC locus of 43 clinical isolates of S. pneumoniae.
Section snippets
Bacterial strains, media and growth conditions
The 43 pneumococcal strains characterized in this study include standard strains D39 (Avery et al., 1944, Iannelli et al., 1999) and 8R1 (Bernheimer, 1979), four strains from the American Type Culture Collection, and 37 recent clinical isolates randomly chosen from an Italian collection (including the type 19F strain G54 whose draft genome sequence is annotated) (Pozzi et al., 1996, Dopazo et al., 2001). Bacteria were grown at 37 °C in tryptic soy broth or tryptic soy agar (Difco) supplemented
PspC nomenclature
The term PspC is preferred over other designations, for two reasons: (i) it was used for the first sequence deposited in GenBank (Accession number: U72655), and (ii) it is a generic name referring only to the surface location of the molecule. Based on deduced amino acid sequence analysis we identified 11 major groups of PspC proteins, and used numbers from 1 to 11 to designate proteins belonging to each group (Fig. 1, see below). Single proteins within each group which display minor variations
Discussion
In this work we characterized the highly polymorphic pspC locus of S. pneumoniae. Sequencing of the pspC locus in 43 pneumococcal isolates allowed comparison with already available pspC sequences, and provided insights into the nature of the pspC gene product, a surface protein important for pathogenesis and vaccine development. Results indicate that: (i) each pneumococcal strain contains a pspC gene at the same chromosomal location, (ii) each pneumococcal strain has a unique DNA sequence at
Acknowledgements
We thank Pat Cleary for critically reading the manuscript. The authors also thank The Institute for Genomic Research (TIGR) for preliminary sequence data of the type 4 S. pneumoniae TIGR4. This work was supported in part by grants from MURST (Cofinanziamento 1999), CNR (P. F. Biotecnologie), and the Commission of the European Union (QLK2-2000-00543).
References (32)
- et al.
The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection
Vaccine
(2000) - et al.
Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function
J. Biol. Chem.
(2000) - et al.
Comparative genomics for identification of clone-specific sequence blocks in Streptococcus pneumoniae
FEMS Microbiol. Lett.
(2001) - et al.
Characterization of cryptic plasmids pDP1 and pSMB1 of Streptococcus pneumoniae
Plasmid
(1999) - et al.
The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells
Cell
(2000) - et al.
Characterization of IS1167, a new insertion sequence in Streptococcus pneumoniae
Plasmid
(1995) - et al.
Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III
J. Exp. Med.
(1944) Lysogenic pneumococci and their bacteriophages
J. Bacteriol.
(1979)- et al.
Pneumococcal diversity: considerations for new vaccine strategies with emphasis on pneumococcal surface protein A (PspA)
Clin. Microbiol. Rev.
(1998) - et al.
The pspC gene of Streptococcus pneumoniae encodes a polymorphic protein, PspC, which elicits cross-reactive antibodies to PspA and provides immunity to pneumococcal bacteremia
Infect. Immun.
(1999)
Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii
Science
Novel purification scheme and functions for a C3-binding protein from Streptococcus pneumoniae
Biochemistry
PspC, a pneumococcal surface protein, binds human factor H
Infect. Immun.
Annotated draft genomic sequence from Streptococcus pneumoniae type 19F clinical isolate
Microb. Drug Resist.
Regulation of NAD metabolism in Salmonella typhimurium: molecular sequence analysis of the bifunctional nadR regulator and the nadA-pnuC operon
J. Bacteriol.
SpsA, a novel pneumococcal surface protein with specific binding to secretory Immunoglobulin A and secretory component
Mol. Microbiol.
Cited by (155)
Recent progress in pneumococcal protein vaccines
2023, Frontiers in ImmunologyIn silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant
2022, Journal of Translational Medicine