Anti-capsular immunity to Streptococcus pneumoniae serotype 22F prevents bacterial transmission in murine colonization and influenza virus co-infection models.
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ABSTRACT:
SUBMITTER: Schmit T
PROVIDER: S-EPMC7877192 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015. Six phylogenetic lineages (n = 117) were identified among a serotype 22F/ST433 clonal complex (CC), including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events.
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Project description:To characterize Streptococcus pneumoniae "serotype 6E," complete cps loci were sequenced. The capsular genes of "serotype 6E" isolates differed much from those of serotypes 6A and 6B. We identified 10 additional "serotype 6E" isolates, which are not confined to a restricted geographic locality. Most of these "serotype 6E" isolates belonged to sequence type 90 and its single-locus variants. The homogeneity of their genetic background and cps loci suggests a recent origin of the "serotype 6E" isolates.
| S-EPMC3811659 | biostudies-literature
Project description:BackgroundStreptococcus pneumoniae is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, that has since become a major public health concern. In this study, the serotypes distribution of pneumococcal isolates was investigated to predict the efficacy of the 7-valent pneumococcal conjugate vaccine (PCV7) among the Malaysian populations.Methodology/principal findingsA total of 151 clinical isolates were serotyped using multiplex PCR assays. Out of them, there were 21.2% penicillin-resistant, 29.1% penicillin-intermediate, and 49.7% penicillin-susceptible S. pneumoniae strains. Serotypes detected among the Malaysian isolates were 1, 3, 10A, 11A/11D, 12F/12A, 14, 15A, 15B/15C, 16F, 18C/18B/18A/18F, 19A, 19F, 23F, 35B, 35F/47F, 6A/6B, 7C/7B/40, 7F/7A, 9V/9A, and 34. Serotype 19F and 23F were the two most prevalent serotypes detected. Serotypes are highly associated with invasiveness of isolates (p?=?0.001) and penicillin susceptibility (p<0.001). Serotype 19F was observed to have increased resistance against penicillin while serotype 19A has high invasive tendency. Age of patients was an important factor underlying the pneumococcal serotypes (p?=?0.03) and clinical sites of infections (p<0.001). High prevalence of pneumococcal isolates were detected among children <5 years old at nasopharyngeal sites while elderly adults ?60 years old were at increased risk for pneumococcal bacteremia.Conclusion/significanceCurrent study revealed that a number of serotypes, especially those associated with high penicillin resistance, have been formulated in the PCV7. Therefore, the protections expected from the routine use of PCV7 would be encouraging for the Malaysian. However, it is not possible to predict serotypes that might become predominant in the future and hence continued surveillance of circulating serotypes will be needed.
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Project description:Understanding the genetic diversification within pneumococcal biofilms.
| PRJNA259232 | ENA
Project description:Streptococcus pneumoniae isolates of serotype 3 were collected from cases of invasive pneumococcal disease (n = 124) throughout Japan between April 2010 and March 2013. A penicillin-resistant S. pneumoniae (PRSP) isolate from an adult patient, strain KK0981 of serotype 3, was identified among these strains. Whole-genome analysis characterized this PRSP as a recombinant strain derived from PRSP of serotype 23F with the cps locus (20.3 kb) replaced by that of a penicillin-susceptible strain of serotype 3.
| S-EPMC5571339 | biostudies-literature
Project description:Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom's childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin--antitoxin systems, were also observed.
| S-EPMC4860696 | biostudies-literature
Project description:UnlabelledStreptococcus pneumoniae colonization of the nasopharynx (NP) is a prerequisite for invasive pneumococcal disease (IPD). The marked reduction in IPD that followed the routine use of pneumococcal polysaccharide conjugate vaccines (PCVs) has been linked to reduced NP colonization with vaccine-included serotypes (STs), with the caveat that PCVs are less effective against pneumonia than against IPD. Although PCV-elicited opsonic antibodies that enhance phagocytic killing of the homologous ST are considered a key correlate of PCV-mediated protection, recent studies question this relationship for some STs, including ST3. Studies with monoclonal antibodies (MAbs) to the pneumococcal capsular polysaccharide (PPS) of ST3 (PPS3) have shown that nonopsonic, as well as opsonic, antibodies can each protect mice against pneumonia and sepsis, but the effect of these types of MAbs on NP colonization is unknown. In this study, we determined the effects of protective opsonic and nonopsonic PPS3 MAbs on ST3 NP colonization in mice. Our results show that a nonopsonic MAb reduced early NP colonization and prevented ST3 dissemination to the lungs and blood, but an opsonic MAb did not. Moreover, the opsonic MAb induced a proinflammatory NP cytokine response, but the nonopsonic MAb had an antiinflammatory effect. The effect of the nonopsonic MAb on colonization did not require its Fc region, but its antiinflammatory effect did. Our findings challenge the paradigm that opsonic MAbs are required to prevent NP colonization and suggest that further studies of the activity of nonopsonic antibodies could advance our understanding of mechanisms of PCV efficacy and provide novel correlates of protection.ImportancePneumococcal conjugate vaccines (PCVs) have markedly reduced the incidence of invasive pneumococcal disease (IPD). Vaccine-elicited pneumococcal polysaccharide (PPS) antibodies that enhance in vitro phagocyte killing of vaccine-included serotypes (STs) (opsonic antibodies) have been considered correlates of vaccine protection and are thought to exert their effect at the initial site of infection, the nasopharynx (NP). However, the data presented here show that this is not the necessarily the case. A nonopsonic PPS monoclonal antibody (MAb) reduced pneumococcal colonization and dissemination of its homologous ST in mice, but surprisingly, an opsonic PPS MAb to the same ST did not. These results reveal that PPS antibodies can work in different ways than previously thought, challenge the paradigm that opsonic antibodies are required to prevent IPD, and provide new insights into PCV efficacy that could lead to novel correlates of vaccine protection.
| S-EPMC4742719 | biostudies-literature
Project description:Recently, Streptococcus pneumoniae serotypes 6C and 6D have been identified. It is thought that they emerged by the replacement of wciN(?) in the capsular loci of serotypes 6A and 6B, respectively. However, their evolution has not been unveiled yet. To investigate the evolution of four serotypes of S. pneumoniae serogroup 6, four genes of the capsular polysaccharide synthesis (cps) locus, wchA, wciN, wciO, and wciP, of isolates of S. pneumoniae serotypes 6A, 6B, 6C, and 6D were sequenced. Multilocus sequence typing (MLST) was performed to investigate their genetic backgrounds. The wchA gene of serotype 6C and 6D isolates was distinct from that of serotype 6A and 6B isolates, which may suggest cotransfer of wchA with wciN(?). Otherwise, serotypes 6C and 6D displayed different genetic backgrounds from serotypes 6A and 6B, which was suggested by MLST analysis. In addition, serotype 6C isolates showed distinct wciP polymorphisms from other serotypes, which also indicated that serotype 6C had not recently originated from serotype 6A. Although serotype 6D shared the same amino acid polymorphisms of wciO with serotype 6B, wciP of serotype 6D differed from that of serotype 6B. The data indicate the implausibility of the scenario of a recent emergence of the cps locus of serotype 6D by genetic recombination between serotypes 6B and 6C. In addition, five serotype 6A and 6B isolates (6X group) displayed cps loci distinct from those of other isolates. The cps locus homogeneity and similar sequence types in MLST analysis suggest that most of the 6X group of isolates originated from the same ancestor and that the entire cps locus might have recently been transferred from an unknown origin. Serotype 6B isolates showed two or more cps locus subtypes, indicating a recombination-mediated mosaic structure of the cps locus of serotype 6B. The collective data favor the emergence of cps loci of serotypes 6A, 6B, 6C, and 6D by complicated recombination.
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Project description:Determination of the capsule type of clinical isolates of Streptococcus pneumoniae is a prerequisite for epidemiological studies and further vaccine development. The Quellung reaction for serotyping is expensive and mostly done in reference centres. We wanted to evaluate whether Fourier-transformed infrared (FT-IR) spectroscopy is suitable for capsular type analysis and prediction of pneumococcal serotypes. We used the IR-Biotyper™ (Bruker) to create a database containing the spectra of 120 strains from invasive disease. The strains covered the 24 vaccine serotypes contained in the 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PSV23). Hierarchical clustering analysis was performed. Finally, two different classification sets were created (PCV13 and PSV23). They were used to predict the serotype of 168 different challenge strains (invasive and non-invasive disease) covering 48 different serotypes (vaccine and non-vaccine types). FT-IR spectra from pneumococci (1300-800 cm-1) clustered along their serotype as determined by the Quellung reaction (120 strains, 24 different serotypes). Strains with unknown serotype fell within the cluster of the correct serotype, as long as the latter was represented in the database (168 strains, 48 different serotypes). Concordance between the Quellung reaction and FT-IR spectroscopy was excellent (kappa ≥ 0.75). FT-IR spectroscopy is a fast and cost-effective method to predict the capsular serotype of pneumococci.
| S-EPMC6778537 | biostudies-literature
Project description:Zwitterionic capsular polysaccharides (ZPS) of commensal bacteria are characterized by having both positive and negative charged substituents on each repeating unit of a highly repetitive structure that has an alpha-helix configuration. In this paper we look at the immune response of CD8(+) T cells to ZPSs. Intraperitoneal application of the ZPS Sp1 from Streptococcus pneumoniae serotype 1 induces CD8(+)CD28(-) T cells in the spleen and peritoneal cavity of WT mice. However, chemically modified Sp1 (mSp1) without the positive charge and resembling common negatively charged polysaccharides fails to induce CD8(+)CD28(-) T lymphocytes. The Sp1-induced CD8(+)CD28(-) T lymphocytes are CD122(low)CTLA-4(+)CD39(+). They synthesize IL-10 and TGF-beta. The Sp1-induced CD8(+)CD28(-) T cells exhibit immunosuppressive properties on CD4(+) T cells in vivo and in vitro. Experimental approaches to elucidate the mechanism of CD8(+) T cell activation by Sp1 demonstrate in a dimeric MHC class I-Ig model that Sp1 induces CD8(+) T cell activation by enhancing crosslinking of TCR. The expansion of CD8(+)CD28(-) T cells is independent, of direct antigen-presenting cell/T cell contact and, to the specificity of the T cell receptor (TCR). In CD8(+)CD28(-) T cells, Sp1 enhances Zap-70 phosphorylation and increasingly involves NF-kappaB which ultimately results in protection versus apoptosis and cell death and promotes survival and accumulation of the CD8(+)CD28(-) population. This is the first description of a naturally occurring bacterial antigen that is able to induce suppressive CD8(+)CD28(-) T lymphocytes in vivo and in vitro. The underlying mechanism of CD8(+) T cell activation appears to rely on enhanced TCR crosslinking. The data provides evidence that ZPS of commensal bacteria play an important role in peripheral tolerance mechanisms and the maintenance of the homeostasis of the immune system.
| S-EPMC2742891 | biostudies-literature