Sequence Analysis and Characterization of a Novel Fibronectin-Binding Repeat Domain from the Surface of<i>Streptococcus pneumoniae</i>

Bumbaca, Daniela; Littlejohn, James; Nayakanti, Hannah; Rigden, Daniel J.; Galperin, Michael Y.; Jedrzejas, Mark J.

doi:10.1089/omi.2004.8.341

Cited by 25 publications

(41 citation statements)

References 57 publications

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“…The spd0080 (spr0075) gene is conserved in other pneumococcus serotypes, and four repeat units have been reported in this gene for serotype 4 strain TIGR4 (110). The repeated amino acids of this unusual protein constitute SSURE domains that bind to the extracellular matrix protein fibrinogen and may play a role in adhesion to eukaryotic host cells (21). PCR analysis using pairs of different primers flanking the repeat regions showed that both D39 strains contain six copies of the repeat (Fig.…”

Section: Resultsmentioning

confidence: 99%

Genome Sequence of Avery's Virulent Serotype 2 Strain D39 ofStreptococcus pneumoniaeand Comparison with That of Unencapsulated Laboratory Strain R6

et al. 2007

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Streptococcus pneumoniae (pneumococcus) is a leading human respiratory pathogen that causes a variety of serious mucosal and invasive diseases. D39 is an historically important serotype 2 strain that was used in experiments by Avery and coworkers to demonstrate that DNA is the genetic material. Although isolated nearly a century ago, D39 remains extremely virulent in murine infection models and is perhaps the strain used most frequently in current studies of pneumococcal pathogenesis. To date, the complete genome sequences have been reported for only two S. pneumoniae strains: TIGR4, a recent serotype 4 clinical isolate, and laboratory strain R6, an avirulent, unencapsulated derivative of strain D39. We report here the genome sequences and new annotation of two different isolates of strain D39 and the corrected sequence of strain R6. Comparisons of these three related sequences allowed deduction of the likely sequence of the D39 progenitor and mutations that arose in each isolate. Despite its numerous repeated sequences and IS elements, the serotype 2 genome has remained remarkably stable during cultivation, and one of the D39 isolates contains only five relatively minor mutations compared to the deduced D39 progenitor. In contrast, laboratory strain R6 contains 71 single-basepair changes, six deletions, and four insertions and has lost the cryptic pDP1 plasmid compared to the D39 progenitor strain. Many of these mutations are in or affect the expression of genes that play important roles in regulation, metabolism, and virulence. The nature of the mutations that arose spontaneously in these three strains, the relative global transcription patterns determined by microarray analyses, and the implications of the D39 genome sequences to studies of pneumococcal physiology and pathogenesis are presented and discussed.Streptococcus pneumoniae (pneumococcus) is a major human respiratory pathogen that causes several serious diseases, including pneumonia, otitis media (ear infection), sinusitis, meningitis, and septicemia (reviewed in references 81, 112, and 114). Invasive pneumococcal diseases result in high rates of mortality and morbidity, especially among young, elderly, debilitated, and immunosuppressed individuals (54, 55). It is estimated that more than 1 million people die each year from pneumococcal infections worldwide, especially in developing countries (59, 80). In the United States and elsewhere, resistance to a range of antibiotics is increasing at an alarming rate among clinical isolates of S. pneumoniae (6, 60). As part of its life cycle, pneumococcus exists as a commensal bacterium that inhabits and colonizes the nasopharynx of up to 20 and 50% of healthy adults and children, respectively, at any time (81, 113). The transition from commensal bacterium to opportunistic pathogen often occurs after another respiratory tract infection.For example, pneumococcal pneumonia has been a leading secondary infection and cause of death during influenza pandemics (9).Strains of S. pneumoniae are categorized into seroty...

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Section: Resultsmentioning

confidence: 99%

Genome Sequence of Avery's Virulent Serotype 2 Strain D39 ofStreptococcus pneumoniaeand Comparison with That of Unencapsulated Laboratory Strain R6

et al. 2007

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“…For example, SP0082, the TIGR4 strain ortholog of PfbB, contains only four of such repeats (21). A detailed bioinformatics analysis of SP0082 was performed by Bumbaca et al (22), who recombinantly expressed the repeat domain and described its ability to interact with Fn, although high concentrations (Ͼ100 g/ml) of the recombinant domain were needed to detect some degree of binding. Because ⌬sp0082 mutants were not generated by these authors, the functional role of this protein or its contribution to the overall Fn binding activity of pneumococci could not be discerned from their data.…”

Section: Discussionmentioning

confidence: 99%

Plasminogen- and Fibronectin-binding Protein B Is Involved in the Adherence of Streptococcus pneumoniae to Human Epithelial Cells

Papasergi

Garibaldi

Tuscano

et al. 2010

Journal of Biological Chemistry

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Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The ability of this bacterium to adhere to epithelial cells is considered as an essential early step in colonization and infection. By screening a whole genome phage display library with sera from infected patients, we previously identified three antigenic fragments matching open reading frame spr0075 of the strain R6 genome. This locus encodes for an ϳ120-kDa protein, herein referred to as plasminogen-and fibronectin-binding protein B (PfbB), which displays an LPXTG cell wall anchoring motif and six repetitive domains. In this study, by using isogenic pfbB-deleted mutants of the encapsulated D39 and of the unencapsulated DP1004 type 2 pneumococcal strains, we show that PfbB is involved in S. pneumoniae adherence to various epithelial respiratory tract cell lines. Our data suggest that PfbB directly mediates bacterial adhesion, because fluorescent beads coated with the recombinant PfbB sp17 fragment (encompassing one of the six repetitive domains and the C-terminal region) efficiently bound to epithelial cells. Mutants lacking PfbB bound to fibronectin and plasminogen considerably less efficiently than wild type bacteria, whereas sp17-coated beads specifically bound to both of these substrates. Taken together, our data suggest that, by directly interacting with fibronectin, PfbB significantly increases the ability of S. pneumoniae to adhere to human epithelial cells.

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“…Bacterial surface proteins bound to Fn form a bridge to ␣ 5 ␤ 1 integrins, which leads to the rearrangement of the cytoskeletal actin in the host cells and the uptake of the bacteria (54,55). S. pneumoniae strain TIGR4 is reported to possess two Fn-binding proteins, PavA and SP0082 (which is equal to SpR0075 in strain R6) (56). Although PavA seems not to function directly as an adhesin, it is probably involved in modulating other as yet unidentified virulence determinants of pneumococci (40).…”

Section: Discussionmentioning

confidence: 99%

PfbA, a Novel Plasmin- and Fibronectin-binding Protein of Streptococcus pneumoniae, Contributes to Fibronectin-dependent Adhesion and Antiphagocytosis

Yamaguchi

Terao

Mori

et al. 2008

Journal of Biological Chemistry

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Streptococcus pneumoniae is a major causative agent of mortality throughout the world. The initial event in invasive pneumococcal disease is the attachment of pneumococci to epithelial cells in the upper respiratory tract. Several bacterial proteins can bind to host extracellular matrix proteins and function as adhesins and invasins. To identify adhesins or invasins on the pneumococcal cell surface, we searched for several proteins with an LPXTG anchoring motif in the whole-genome sequence of Streptococcus pneumoniae and identified one, which we called PfbA (plasmin-and fibronectin-binding protein A), that bound to human serum proteins. Immunofluorescence microscopy and fluorescence-activated cell sorter analysis revealed that PfbA was expressed on the pneumococcal cell surface. A ⌬pfbA mutant strain was only half as competent as the wild-type strain at adhering to and invading lung and laryngeal epithelial cells. In addition, epithelial cells infected with ⌬pfbA showed morphological changes, including cell flattening and a loss of microvilli, that did not occur in cells infected with the wild-type strain. The mutant strain also exhibited a weaker antiphagocytotic activity than wild type in human peripheral blood. Moreover, the growth of wild-type bacteria in human whole blood containing anti-PfbA antibodies was reduced by ϳ50% after 3 h compared with its growth without the antibody. These results suggest that PfbA is an important factor in the development of pneumococcal infections.

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Sequence Analysis and Characterization of a Novel Fibronectin-Binding Repeat Domain from the Surface ofStreptococcus pneumoniae

Cited by 25 publications

References 57 publications

Genome Sequence of Avery's Virulent Serotype 2 Strain D39 ofStreptococcus pneumoniaeand Comparison with That of Unencapsulated Laboratory Strain R6

Genome Sequence of Avery's Virulent Serotype 2 Strain D39 ofStreptococcus pneumoniaeand Comparison with That of Unencapsulated Laboratory Strain R6

Plasminogen- and Fibronectin-binding Protein B Is Involved in the Adherence of Streptococcus pneumoniae to Human Epithelial Cells

PfbA, a Novel Plasmin- and Fibronectin-binding Protein of Streptococcus pneumoniae, Contributes to Fibronectin-dependent Adhesion and Antiphagocytosis

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