scholarly journals The crystal structure of the estA protein, a virulence factor from Streptococcus pneumoniae

2007 ◽  
Vol 70 (2) ◽  
pp. 578-583 ◽  
Author(s):  
Myung Hee Kim ◽  
Beom Sik Kang ◽  
Sujin Kim ◽  
Kyung-Jin Kim ◽  
Choong Hwan Lee ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Streptococcus Pneumoniae ◽  
Virulence Factor ◽  
Protein A

scholarly journals Invasive Streptococcus pneumoniae isolates from Argentinian children: serotypes, families of pneumococcal surface protein A (PspA) and genetic diversity

2004 ◽  
Vol 132 (2) ◽  
pp. 177-184 ◽  
Author(s):  
M. MOLLERACH ◽  
M. REGUEIRA ◽  
L. BONOFIGLIO ◽  
R. CALLEJO ◽  
J. PACE ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Streptococcus Pneumoniae ◽  
Virulence Factor ◽  
Protein A ◽  
Surface Protein ◽  
Potential Candidate ◽  
The World ◽  
Effective Development ◽  
Complement Deposition ◽  
Optimal Protection

PspA is an antigenically variable virulence factor of Streptococcus pneumoniae that inhibits complement deposition and is a potential candidate for human vaccines. Of 64 published strains 96% are in PspA families 1 and 2; optimal protection is family-specific. Effective development of a PspA-containing vaccine requires more information about the PspA family of strains in parts of the world where the vaccine is most needed. In these studies we observed that of 149 isolates (of 19 capsular types) from Argentina, 54·4% were family 1, 41·6% were family 2 and 4·0% expressed both family 1 and family 2 PspAs. Box typing revealed the Argentinian strains to be from at least 10 clonally related groups.

scholarly journals Comparison of the PspA Sequence from Streptococcus pneumoniae EF5668 to the Previously Identified PspA Sequence from Strain Rx1 and Ability of PspA from EF5668 To Elicit Protection against Pneumococci of Different Capsular Types

1998 ◽  
Vol 66 (10) ◽  
pp. 4748-4754 ◽  
Author(s):  
Larry S. McDaniel ◽  
D. Olga McDaniel ◽  
Susan K. Hollingshead ◽  
David E. Briles
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antibody Response ◽  
Dna Sequence ◽  
Virulence Factor ◽  
Selective Pressure ◽  
Protein A ◽  
Surface Protein ◽  
Laboratory Strain ◽  
Cross Protection ◽  
Gene Encoding

ABSTRACT PspA (pneumococcal surface protein A) is a serologically varied virulence factor of Streptococcus pneumoniae. In mice, PspA has been shown to elicit an antibody response that protects against fatal challenge with encapsulated S. pneumoniae, and the protection-eliciting residues have been mapped to the α-helical N-terminal half of the protein. To date, a published DNA sequence forpspA is available only for S. pneumoniae Rx1, a laboratory strain. PspA/EF5668 (EF5668 indicates the strain of origin of the PspA) is serologically distinct from PspA/Rx1. Sequencing of the gene encoding PspA/EF5668 revealed 71% identity with that of PspA/Rx1. The greatest amount of divergence between the two proteins was seen in their α-helical portions, which are surface exposed and probably under selective pressure to diversify serologically. In spite of the diversity within the α-helical regions of PspAs, we have observed that recombinant PspA (rPspA)/EF5668, like rPspA/Rx1, can elicit cross-protection against pneumococci of different capsular and PspA serological types.

scholarly journals Crystal structure of an active form of RAS protein, a complex of a GTP analog and the HRAS p21 catalytic domain.

1990 ◽  
Vol 87 (12) ◽  
pp. 4849-4853 ◽  
Author(s):  
A. T. Brunger ◽  
M. V. Milburn ◽  
L. Tong ◽  
A. M. deVos ◽  
J. Jancarik ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Domain ◽  
Active Form ◽  
Protein A ◽  
Ras Protein

scholarly journals Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Hannah L. Turkington ◽  
Mindaugas Juozapaitis ◽  
Nikos Tsolakos ◽  
Eugenia Corrales-Aguilar ◽  
Martin Schwemmle ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Virulence Factor ◽  
Influenza A ◽  
Nonstructural Protein ◽  
Functional Divergence ◽  
Protein A ◽  
Regulatory Subunit ◽  
Ns1 Protein ◽  
Influenza A Viruses ◽  
Hydrophobic Patch

ABSTRACT Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species.

scholarly journals Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain ofStaphylococcus aureusFibronectin-Binding Protein A

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e00590-17
Author(s):  
P. Martijn den Reijer ◽  
Mehri Tavakol ◽  
Nicole Lemmens-den Toom ◽  
Dikra Allouch ◽  
Sheila Thomas ◽  
...  
Keyword(s):  
Antibody Response ◽  
Virulence Factor ◽  
Antibody Production ◽  
Immunoglobulin G ◽  
Binding Protein ◽  
Protein A ◽  
Sequence Diversity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Antibody ◽  
Fibrinogen Binding

ABSTRACTThe fibronectin-binding protein A (FnBPA) is a cell surface-associated protein ofStaphylococcus aureuswhich mediates adherence to the host extracellular matrix and is important for bacterial virulence. Previously, substantial sequence diversity was found among strains in the fibrinogen-binding A domain of this protein, and 7 different isotypes were described. The effect of this sequence diversity on the human antibody response, in terms of both antibody production and antibody function, remains unclear. In this study, we identify five different FnBPA A domain isotypes based on the sequence results of 22 clinicalS. aureusisolates, obtained from the same number of patients suffering from bacteremia. Using a bead-based Luminex technique, we measure the patients’ total immunoglobulin G (IgG) against the 7 FnBPA isotypes at the onset and during the time course of bacteremia (median of 10 serum samples per patient over a median of 35 days). A significant increase in IgG against the FnBPA A domain, including the isotype carried by the infecting strain, is observed in only three out of 22 patients (14%) after the onset of bacteremia. Using a Luminex-based FnBPA–fibrinogen-binding assay, we find that preincubation of recombinant FnBPA isotypes with IgG from diverse patients does not interfere with binding to fibrinogen. This observation is confirmed using an alternative Luminex-based assay and enzyme-linked immunosorbent assay (ELISA).IMPORTANCEDespite the manyin vitroand murinein vivostudies involving FnBPA, the actual presence of this virulence factor during human infection is less well established. Furthermore, it is currently unknown to what extent sequence variation in such a virulence factor affects the human antibody response and the ability of antibodies to interfere with FnBPA function. This study sheds new light on these issues. First, the uniform presence of a patient’s IgG against FnBPA indicates the presence and importance of this virulence factor duringS. aureuspathogenesis. Second, the absence of an increase in antibody production in most patients following bacteremia indicates the complexity ofS. aureus-host interactions, possibly involving immune evasion or lack of expression of FnBPA during invasive infection. Finally, we provide new insights into the inability of human antibodies to interfere with FnBPA-fibrinogen binding. These observations should be taken into account during the development of novel vaccination approaches.

scholarly journals DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein

2006 ◽  
Vol 55 (4) ◽  
pp. 375-378 ◽  
Author(s):  
Daniela M. Ferreira ◽  
Eliane N. Miyaji ◽  
Maria Leonor S. Oliveira ◽  
Michelle Darrieux ◽  
Ana Paula M. Arêas ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Recombinant Protein ◽  
Dna Vaccines ◽  
Protein A ◽  
Surface Protein ◽  
Humoral Response ◽  
Cost Effective ◽  
Promising Candidate ◽  
Pneumococcal Surface Protein A ◽  
Antibody Levels

Pneumococcal surface protein A (PspA) is a promising candidate for the development of cost-effective vaccines against Streptococcus pneumoniae. In the present study, BALB/c mice were immunized with DNA vaccine vectors expressing the N-terminal region of PspA. Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol. However, both immunogens elicited similar levels of protection against intraperitoneal challenge. Furthermore, immunization with exactly the same fragment in the form of a recombinant protein, with aluminium hydroxide as an adjuvant, elicited even higher antibody levels, but this increased humoral response did not correlate with enhanced protection. These results show that DNA vaccines expressing PspA are able to elicit protection levels comparable to recombinant protein, even though total anti-PspA IgG response is considerably lower.

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