New Pneumococcal Serotype 15D.
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ABSTRACT:
SUBMITTER: Pimenta F
PROVIDER: S-EPMC8091843 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
New Pneumococcal Serotype 15D.
Pimenta Fabiana F Moiane Benild B Gertz Robert E RE Chochua Sopio S Snippes Vagnone Paula M PM Lynfield Ruth R Sigaúque Betuel B Carvalho Maria da Gloria MDG Beall Bernard B
Journal of clinical microbiology 20210420 5
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Project description:We have recently reported a new pneumococcal serotype (6C), which is closely related to serotype 6A (I. H. Park et al., J. Clin. Microbiol. 45:1225-1233, 2007). To investigate the genetic basis for serotype 6C, we studied the capsule gene loci of 14 6C isolates from three different continents, including one isolated in Alabama 27 years ago. The wciN region of all 6C isolates has a 1,029-bp-long sequence that replaces the 1,222-bp-long sequence of the 6A wciN region. This recombination event has created a new 1,125-bp-long open reading frame which encodes a product that is also homologous to glycosyl transferases. Flanking this introduced gene is 300 bp upstream and 100 bp downstream with only about 90% homology with 6A and which is identical in all 6C isolates. Transfer of the wciN region converts 6A to 6C. Determination of the DNA sequence of the entire capsule gene locus of one 6C isolate showed that the 6C capsule gene locus is almost identical (>98% homologous) to that of 6A except for the wciN region. These findings indicate that the 6C capsule type originated more than 27 years ago by a single recombination event in a 6A locus in which 6A wciN was replaced by a gene of unknown origin.
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Project description:The polysaccharide (PS) capsule of Streptococcus pneumoniae (pneumococcus) is the immunodominant surface structure that shields the bacteria from the host immune system. Since the capsule is the primary target of currently available pneumococcal vaccines, anti-capsular antibodies are highly protective but serotype-specific. Pneumococci may evade host or vaccine-induced immunity as a result of variation in capsule structure mediated via multiple mechanisms, such as the loss or gain of O-acetylation. Previous biochemical studies of serogroup 20 isolates have identified two subtypes-20A and 20B, whose capsule PS differs in the WhaF-mediated glucose side chain. Herein, we characterize a newly discovered capsule type, 20C, that differs from serotype 20B via the inactivation of capsule O-acetyltransferase gene, wciG. Structural analysis demonstrated that 20C and 20B share an identical repeat unit [→3)-α-D-GlcpNAc-[β-D-Galf-(1→4)][α-D-Glcp-(1→6)]-(1→P→6)-α-D-Glcp-(1→6)- β-D-Glcp-(1→3)-β-D-Galf 5,6Ac2-(1→3)-β-D-Glcp-(1→], except for the absence of WciG-mediated O-acetyl group at terminal galactofuranose (β-D-Galf). We confirmed that deletion of the wciG gene in a 20B strain resulted in the expression of the 20C capsule. Serotype 20C is serologically indistinguishable from the canonical 20A and 20B using conventional serotyping antibodies, but serogroup 20 subtypes can be distinguished by sequencing of cps genes-whaF, wciG, and wcjE. While genetic screening suggests 20C to be globally less prevalent, a new variant was identified which appears to have both wciG and whaF genes inactive, potentially indicating it to be a new serotype. Consequently, genome-based serotyping/bioinformatic tools must scrutinize all cps genes for mutations that might inactivate/modify cps-encoded enzymes, ensuring effective tracking of emerging capsule variants in response to ongoing vaccination efforts.ImportanceStreptococcus pneumoniae (pneumococcus) is a significant human pathogen known for producing a wide array of antigenically and structurally diverse capsule types, a fact that poses a serious challenge to the effectiveness of vaccines targeting pneumococcal capsule polysaccharide (PS). Herein, we provide a comprehensive analysis-genetic, antigenic, and biochemical of a newly identified capsule type, 20C, which differs from the canonical serotype 20B due to the inactivation of the capsule O-acetyltransferase gene, wciG. Our findings highlight how pneumococci can alter their capsule PS structure and immunological characteristics through minor genetic modifications. Since the appearance of new capsule types can directly affect pneumococcal conjugate vaccine (PCV) implementation, a deeper understanding of capsule PS at the genetic, immunological, and biochemical levels is critical for the development of future diagnostic tools and vaccines.
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Project description:Recently, 2 serologically and biochemically distinct subtypes-11Aalpha and 11Abeta-were discovered among serotype 11A isolates of Streptococcus pneumoniae. Sequence comparison of the capsular polysaccharide synthesis (cps) loci of the 2 subtypes identified disruption of the wcjE gene, a putative O-acetyltransferase, as the genetic hallmark of the 11Abeta phenotype. Directed disruption of wcjE in vitro in an 11Aalpha strain switched the strain to the 11Abeta phenotype, confirming the role played by the gene in the divergence between the subtypes. Furthermore, sequences from 7 11Abeta clinical strains each contained unrelated disruptive mutations in the wcjE gene, displaying an unprecedented degree of genetic heterogeneity in a pneumococcal serotype. We propose to name the 11Aalpha subtype as serotype 11A and the 11Abeta subtype as 11E, a new serotype. Our findings also suggest that the diversity of pneumococcal capsules is much greater than was previously recognized.
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Project description:Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children <5 years of age by 75%. However, due to replacement through herd effects, the decrease among the older population is predicted to be much less (20-40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including new serotypes in the vaccine (e.g. 22 and 9N).
| S-EPMC3923658 | biostudies-literature
Project description:BackgroundStreptococcus pneumoniae (pneumococcus) causes invasive pneumococcal disease (IPD) and non-invasive acute respiratory infections (ARIs). Three pneumococcal conjugate vaccines (PCVs) are recommended in the United States with additional products in clinical trials. We aimed to estimate 1) proportions of IPD cases and pneumococcal ARIs caused by serotypes targeted by existing and pipeline PCVs and 2) annual U.S. pneumococcal burdens potentially preventable by PCVs.MethodsWe estimated serotype distribution and proportions of non-invasive pneumococcal ARIs (AOM [children only], sinusitis, non-bacteremic pneumonia) and IPD attributable to serotypes targeted by each PCV using Markov chain Monte Carlo approaches incorporating data from studies of serotype distribution in ARIs and Active Bacterial Core Surveillance (ABCs) data. We then estimated annual numbers of outpatient-managed pneumococcal ARIs, non-bacteremic pneumococcal pneumonia hospitalizations, and IPD cases potentially preventable by PCVs in the United States by multiplying pneumococcal disease incidence rates by PCV-targeted proportions of disease and vaccine effectiveness estimates.ResultsIn children, PCV15, PCV20, PCV24, PCV25, and PCV31 serotypes account for 16% (95% confidence interval: 15-17%), 31% (30-32%), 34% (32-35%), 43% (42-44%), and 68% (67-69%) of pneumococcal acute otitis media cases, respectively. In adults, PCV15, PCV20, PCV21, PCV24, PCV25, and PCV31 serotypes account for 43% (38-47%), 52% (47-57%), 69% (64-73%), 65% (61-70%), 62% (57-67%), and 87% (83-90%) of pneumococcal non-bacteremic pneumonia cases. For IPD, 42-85% of pediatric and 42-94% of adult cases were due to PCV-targeted serotypes. PCV-preventable burdens encompassed 270 thousand-3.3 million outpatient-managed ARIs, 2-17 thousand non-bacteremic pneumonia hospitalizations, and 3-14 thousand IPD cases in the United States annually.ConclusionsAcross pneumococcal conditions, coverage and preventable burdens were lowest for PCV15 and highest for PCV31, with PCV21 also targeting sizeable burdens of adult disease. Serotype distribution across syndromes may inform vaccine formulations and policy.
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Project description:The bacterial pathogen Streptococcus pneumoniae expresses one of over 90 structurally distinct polysaccharide (PS) capsule serotypes. Prior PS structural analyses of the vaccine-associated serotype 20 do not agree with reports describing the genes that mediate capsule synthesis. Furthermore, using immunized human sera-based assays, serological differences were recently noted among strains typed as serotype 20. We examined the capsule structures of two serologically dissimilar serotype 20 strains, 20? and 20?, by extensive biochemical analysis. 20? PS was composed of the previously described serotype 20 hexasaccharide repeat unit, whereas the 20? PS was composed of a novel heptasaccharide repeat unit containing an extra branching ?-glucose residue. Genetic analysis of the subtypes revealed that 20? may have arisen from a 20? progenitor following loss of function mutation to the glycosyltransferase gene whaF. Conventional serotyping methods using rabbit polyclonal or mouse monoclonal antibodies were unable to distinguish the subtypes. However, genetic analysis of multiple "serotype 20" clinical isolates revealed that all strains contain the 20? genotype. We propose naming bacteria that express the previously described 20? capsule structure 20A and bacteria that express the novel 20? capsule structure 20B, a new pneumococcal serotype.
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Project description:Streptococcus pneumoniae clinical isolates were recently described that produced capsular polysaccharide with properties of both serotypes 6A and 6B. Their hybrid serological property correlated with mutations affecting the glycosyltransferase WciP, which links rhamnose to ribitol by an α(1-3) linkage for serotypes 6A and 6C and an α(1-4) linkage for serotypes 6B and 6D. The isolates had mutations in the triad residues of WciP that have been correlated with enzyme specificity. The canonical triad residues of WciP are Ala192-Ser195-Arg254 for serotypes 6A and 6C and Ser192-Asn195-Gly254 for serotypes 6B and 6D. To prove that the mutations in the triad residues are responsible for the hybrid serotype, we introduced the previously described Ala192-Cys195-Arg254 triad into a 6A strain and found that the change made WciP bispecific, resulting in 6A and 6B repeat unit expression, although 6B repeat unit production was favored over production of 6A repeat units. Likewise, this triad permitted a 6C strain to express 6C and 6D repeat units. With reported bispecificity in WciN, which adds either glucose or galactose as the second sugar in the serogroup 6 repeat unit, the possibility exists for a strain to simultaneously produce all four serogroup 6 repeat units; however, when genes encoding both bispecific enzymes were introduced into a 6A strain, only 6A, 6B, and 6D repeat units were detected serologically. Nonetheless, this may be the first example of a bacterial polysaccharide with three different repeat units. This strategy of expressing multiple repeat units in a single polymer is a novel approach to broadening vaccine coverage by eliminating the need for multiple polysaccharide sources to cover multiple serogroup members.
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Project description: Not available
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