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  • 1
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    Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen
    American Society for Microbiology ; 2017
    In:  Infection and Immunity Vol. 85, No. 10 ( 2017-10)
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 85, No. 10 ( 2017-10)
    Abstract: Serotype-specific protection against Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from Salmonella enterica serovar Typhimurium displaying the variable N terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.00281-17
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
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  • 2
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    Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion
    American Society for Microbiology ; 2018
    In:  Infection and Immunity Vol. 86, No. 4 ( 2018-04)
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 86, No. 4 ( 2018-04)
    Abstract: The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC . The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.00010-18
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2018
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  • 3
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    The HLA A03 Supertype and Several Pan Species Major Histocompatibility Complex Class I A Allotypes Share a Preference for Binding Positively Charged Residues in the F Pocket: Implications for Controlling Retroviral Infections
    American Society for Microbiology ; 2020
    In:  Journal of Virology Vol. 94, No. 9 ( 2020-04-16)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 94, No. 9 ( 2020-04-16)
    Abstract: The major histocompatibility complex (MHC) class I region of humans, chimpanzees ( Pan troglodytes ), and bonobos ( Pan paniscus ) is highly similar, and orthologues of HLA-A , - B , and - C are present in both Pan species. Based on functional characteristics, the different HLA-A allotypes are classified into different supertypes. One of them, the HLA A03 supertype, is widely distributed among different human populations. All contemporary known chimpanzee and bonobo MHC class I A allotypes cluster genetically into one of the six HLA-A families, the HLA-A1/A3/A11/A30 family. We report here that the peptide-binding motif of the Patr-A*05:01 allotype, which is commonly present in a cohort of western African chimpanzees, has a strong preference for binding peptides with basic amino acids at the carboxyl terminus. This phenomenon is shared with the family members of the HLA A03 supertype. Based on the chemical similarities in the peptide-binding pocket, we inferred that the preference for binding peptides with basic amino acids at the carboxyl terminus is widely present among the human, chimpanzee, and bonobo MHC-A allotypes. Subsequent in silico peptide-binding predictions illustrated that these allotypes have the capacity to target conserved parts of the proteome of human immunodeficiency virus type 1 (HIV-1) and the simian immunodeficiency virus SIVcpz. IMPORTANCE Most experimentally infected chimpanzees seem to control an HIV-1 infection and are therefore considered to be relatively resistant to developing AIDS. Contemporary free-ranging chimpanzees may carry SIVcpz, and there is evidence for AIDS-like symptoms in these free-ranging animals, whereas SIV infections in bonobos appear to be absent. In humans, the natural control of an HIV-1 infection is strongly associated with the presence of particular HLA class I allotypes. The ancestor of the contemporary living chimpanzees and bonobos survived a selective sweep targeting the MHC class I repertoire. We have put forward a hypothesis that this may have been caused by an ancestral retroviral infection similar to SIVcpz. Characterization of the relevant MHC allotypes may contribute to understanding the shaping of their immune repertoire. The abundant presence of MHC-A allotypes that prefer peptides with basic amino acids at the C termini suggests that these molecules may contribute to the control of retroviral infections in humans, chimpanzees, and bonobos.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01960-19
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1495529-5
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  • 4
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    Differential Protein Expression in Phenotypic Variants of Streptococcus pneumoniae
    American Society for Microbiology ; 2000
    In:  Infection and Immunity Vol. 68, No. 8 ( 2000-08), p. 4604-4610
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 68, No. 8 ( 2000-08), p. 4604-4610
    Abstract: Streptococcus pneumoniae undergoes spontaneous phase variation resulting in opaque and transparent colony forms. Differences in colony opacity correlate with differences in virulence: the transparent variants are more capable of colonizing the nasopharynx, whereas the opaque variants show increased virulence during systemic infections. To gain insight into the pathogenesis of pneumococcal disease at the molecular level, protein expression patterns of the phenotypic variants of two pneumococcal strains were compared by high-resolution two-dimensional protein electrophoresis. In comparison with transparent variants, the opaque variants reduced the expression of two proteins and overexpressed one protein. The proteins were identified by mass spectrometric analysis. The protein overexpressed in the opaque phenotype revealed significant homology to elongation factor Ts of Helicobacter pylori . One of the two proteins that were underexpressed in the opaque variants revealed significant homology to the proteinase maturation protein PrtM of Lactocobacillus paracasei , a member of the family of peptidyl-prolyl cis/trans isomerases. A consensus lipoprotein signal sequence suggests that the putative proteinase maturation protein A, designated PpmA, is located at the surface of the pneumococcus and may play a role in the maturation of surface or secreted proteins. The second underexpressed protein was identified as pyruvate oxidase, SpxB. The lower SpxB expression in opaque variants most probably explains the reduced production of hydrogen peroxide, a reaction product of SpxB, in this variant. Since a spxB -defective pneumococcal mutant has decreased ability to colonize the nasopharynx (B. Spellerberg, D. R. Cundell, J. Sandros, B. J. Pearce, I. Idanpaan-Heikkila, C. Rosenow, and H. R. Masure, 1996. Mol. Microbiol. 19:803–813, 1996), our data suggest that SpxB plays an important role in enhancing the ability of transparent variants to efficiently colonize the nasopharynx.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.68.8.4604-4610.2000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2000
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  • 5
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    CodY of Streptococcus pneumoniae : Link between Nutritional Gene Regulation and Colonization
    American Society for Microbiology ; 2008
    In:  Journal of Bacteriology Vol. 190, No. 2 ( 2008-01-15), p. 590-601
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 190, No. 2 ( 2008-01-15), p. 590-601
    Abstract: CodY is a nutritional regulator mainly involved in amino acid metabolism. It has been extensively studied in Bacillus subtilis and Lactococcus lactis . We investigated the role of CodY in gene regulation and virulence of the human pathogen Streptococcus pneumoniae . We constructed a codY mutant and examined the effect on gene and protein expression by microarray and two-dimensional differential gel electrophoresis analysis. The pneumococcal CodY regulon was found to consist predominantly of genes involved in amino acid metabolism but also several other cellular processes, such as carbon metabolism and iron uptake. By means of electrophoretic mobility shift assays and DNA footprinting, we showed that most of the targets identified are under the direct control of CodY. By mutating DNA predicted to represent the CodY box based on the L. lactis consensus, we demonstrated that this sequence is indeed required for in vitro DNA binding to target promoters. Similar to L. lactis , DNA binding of CodY was enhanced in the presence of branched-chain amino acids, but not by GTP. We observed in experimental mouse models that codY is transcribed in the murine nasopharynx and lungs and is specifically required for colonization. This finding was underscored by the diminished ability of the codY mutant to adhere to nasopharyngeal cells in vitro. Furthermore, we found that pcpA , activated by CodY, is required for adherence to nasopharyngeal cells, suggesting a direct link between nutritional regulation and adherence. In conclusion, pneumococcal CodY predominantly regulates genes involved in amino acid metabolism and contributes to the early stages of infection, i.e., colonization of the nasopharynx.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.00917-07
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2008
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 6
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    Persistence of Clones of Coagulase-Negative Staphylococci among Premature Neonates in Neonatal Intensive Care Units: Two-Center Study of Bacterial Genotyping and Patient Risk Factors
    American Society for Microbiology ; 1998
    In:  Journal of Clinical Microbiology Vol. 36, No. 9 ( 1998-09), p. 2485-2490
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 36, No. 9 ( 1998-09), p. 2485-2490
    Abstract: From 1 January 1995 until 1 January 1996, we studied the molecular epidemiology of blood isolates of coagulase-negative staphylococci (CoNS) in the Neonatal Intensive Care Units (NICUs) of the Sophia Children’s Hospital (SCH; Rotterdam, The Netherlands) and the Wilhelmina Children’s Hospital (WCH; Utrecht, The Netherlands). The main goal of the present study was to detect putatively endemic clones of CoNS persisting in these NICUs. Pulsed-field gel electrophoresis was used to detect the possible presence of endemic clones of clinical significance. In addition, clinical data of patients in the SCH were analyzed retrospectively to identify risk factors for the acquisition of positive blood cultures. In both centers, endemic CoNS clones were persistently present. Thirty-three percent of the bacterial isolates derived from blood cultures in the SCH belonged to a single genotype. In the WCH, 45% of all bacterial strains belonged to a single clone. These clones were clearly different from each other, which implies that site specificity is involved. Interestingly, we observe that the clonal type in the SCH differed significantly from the incidentally occurring strains with respect to both the average pH and partial CO 2 pressure of the patient’s blood at the time of bacterial culture. We found that the use of intravascular catheters, low gestational age, and a long hospital stay were important risk factors for the development of a putative CoNS infection. When the antibiotic susceptibility of the bacterial isolates was assessed, a clear correlation between the nature of the antibiotics most frequently used as a first line of defense versus the resistance profile was observed. We conclude that the intensive use of antibiotics in an NICU setting with highly susceptible patients causes selection of multiresistant clones of CoNS which subsequently become endemic.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.36.9.2485-2490.1998
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1998
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 7
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    Multidrug-Resistant Streptococcus pneumoniae in Poland: Identification of Emerging Clones
    American Society for Microbiology ; 1999
    In:  Journal of Clinical Microbiology Vol. 37, No. 6 ( 1999-06), p. 1739-1745
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 37, No. 6 ( 1999-06), p. 1739-1745
    Abstract: Penicillin resistance among Streptococcus pneumoniae isolates has rapidly emerged in Poland during the last decade and has reached prevalence levels of up to 14.4% in 1997. In order to investigate the nature of this increase, a molecular epidemiological analysis of non-penicillin-susceptible multidrug-resistant pneumococci isolated in 1995 and 1996 was conducted. Thirty-seven patients who suffered mainly from upper respiratory tract infections and pneumococcal pneumonia were enrolled in this study. The medical centers to which the patients were admitted were located in 16 Polish towns across the country. Eight distinct BOX PCR types were observed, representing 14 subtypes. Restriction fragment end labeling (RFEL) analysis divided the pneumococcal strains into 16 distinct types. By combining the BOX PCR and RFEL data, four genetically distinct clusters of strains were identified. Two clusters represented the genetic clones 23F and 9V, which have recently emerged all over the world. The two other genetic clusters, which represented serotypes 23F and 6B, clearly predominated in the analyzed collection of Polish non-penicillin-susceptible pneumococcal strains. Since the latter clusters did not match any of the 133 RFEL types of non-penicillin-susceptible pneumococci collected in 15 other countries, their Polish clonal origin is most likely.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.37.6.1739-1745.1999
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1999
    detail.hit.zdb_id: 1498353-9
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  • 8
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    Complement Activation in Relation to Capillary Leakage in Children with Septic Shock and Purpura
    American Society for Microbiology ; 1998
    In:  Infection and Immunity Vol. 66, No. 11 ( 1998-11), p. 5350-5356
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 66, No. 11 ( 1998-11), p. 5350-5356
    Abstract: To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A 2 , and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times high er in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.66.11.5350-5356.1998
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1998
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  • 9
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    Pneumococcal Carriage in Children in The Netherlands: a Molecular Epidemiological Study
    American Society for Microbiology ; 2001
    In:  Journal of Clinical Microbiology Vol. 39, No. 9 ( 2001-09), p. 3316-3320
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 39, No. 9 ( 2001-09), p. 3316-3320
    Abstract: In 1999, Engelen and coworkers investigated colonization in Amsterdam among 259 children attending 16 day-care centers (DCCs) and among 276 children who did not attend day-care centers (NDCCs). A 1.6- to 3.4-fold increased risk for nasopharyngeal colonization was observed in children attending DCCs compared with NDCC children, while no difference in antibiotic resistance was found between groups. The serotype and genotype distributions of 305 nasopharyngeal Streptococcus pneumoniae isolates of the latter study were investigated. The predominant serotypes in both the DCC and the NDCC groups included 19F (19 and 18%, respectively), 6B (14 and 16%, respectively), 6A (13 and 7%, respectively), 23F (9 and 7%, respectively), and 9V (7 and 7%, respectively). The theoretical vaccine coverage of the 7-valent conjugate vaccine was 59% for the DCC children and 56% for the NDCC group. Genetic analysis of the pneumococcal isolates revealed 75% clustering among pneumococci isolated from DCC attendees versus 50% among the NDCC children. The average pneumococcal cluster size in the DCC group was 3.8 and 4.6 isolates for two respective sample dates (range, 2 to 13 isolates per cluster), while the average cluster size for the NDCC group was 3.0 (range, 2 to 6 isolates per cluster). Similar to observations made in other countries, these results indicate a higher risk for horizontal spread of pneumococci in Dutch DCCs than in the general population. This study emphasizes the importance of molecular epidemiological monitoring before, during, and after implementation of pneumococcal conjugate vaccination in national vaccination programs for children.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.39.9.3316-3320.2001
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 10
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    Host-Pathogen Interaction during Pneumococcal Infection in Patients with Chronic Obstructive Pulmonary Disease
    American Society for Microbiology ; 2004
    In:  Infection and Immunity Vol. 72, No. 2 ( 2004-02), p. 818-823
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 72, No. 2 ( 2004-02), p. 818-823
    Abstract: Acute exacerbation is a frequent complication of chronic obstructive pulmonary disease (COPD). Recent studies suggested a role for bacteria such as Streptococcus pneumoniae in the development of acute exacerbation. For this study, we investigated the following in COPD patients: (i) the epidemiology of pneumococcal colonization and infection, (ii) the effect of pneumococcal colonization on the development of exacerbation, and (iii) the immunological response against S. pneumoniae . We cultured sputa of 269 COPD patients during a stable state and during exacerbation of COPD and characterized 115 pneumococcal isolates by use of serotyping. Moreover, we studied serum immunoglobulin G (IgG) antibody titers, antibody avidities, and functional antibody titers against the seven conjugate vaccine serotypes in these patients. Colonization with only pneumococci (monocultures) increased the risk of exacerbation, with a hazard ratio of 2.93 (95% confidence interval, 1.41 to 6.07). The most prevalent pneumococcal serotypes found were serotypes 19F, 3, 14, 9L/N/V, 23A/B, and 11. We calculated the theoretical coverage for the 7- and 11-valent pneumococcal vaccines to be 60 and 73%, respectively. All patients had detectable IgG levels against the seven conjugate vaccine serotypes. These antibody titers were significantly lower than those in vaccinated healthy adults. Finally, on average, a 2.5-fold rise in serotype-specific and functional antibodies in S. pneumoniae -positive sputum cultures was observed during exacerbation. Our data indicate that pneumococcal colonization in COPD patients is frequently caused by vaccine serotype strains. Moreover, pneumococcal colonization is a risk factor for exacerbation of COPD. Finally, our findings demonstrate that COPD patients are able to mount a significant immune response to pneumococcal infection. COPD patients may therefore benefit from pneumococcal vaccination.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.72.2.818-823.2004
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
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