Pneumococcal Vaccines: Host Interactions, Population Dynamics, and Design Principles

Croucher, Nicholas J.; Løchen, Alessandra; Bentley, Stephen D.

doi:10.1146/annurev-micro-090817-062338

Cited by 50 publications

(70 citation statements)

References 200 publications

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“…The opportunistic human pathogen Streptococcus pneumoniae (the pneumococcus) kills over a million individuals each year, despite the introduction of several vaccines targeting its capsule (Croucher et al, 2018;O'Brien et al, 2009;Prina et al, 2015). Because of its ability to take up DNA from its environment by competence activation, genes associated with capsule biosynthesis are rapidly transferred from one strain to the other thereby contributing to vaccine escape (Salvadori et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Unbiased homeologous recombination during pneumococcal transformation allows for multiple chromosomal integration events

Kurushima

Campo

Raaphorst

et al. 2020

eLife

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The spread of antimicrobial resistance and vaccine escape in the human pathogen Streptococcus pneumoniae can be largely attributed to competence-induced transformation. Here, we studied this process at the single-cell level. We show that within isogenic populations, all cells become naturally competent and bind exogenous DNA. We find that transformation is highly efficient and that the chromosomal location of the integration site or whether the transformed gene is encoded on the leading or lagging strand has limited influence on recombination efficiency. Indeed, we have observed multiple recombination events in single recipients in real-time. However, because of saturation and because a single stranded donor DNA replaces the original allele, transformation efficiency has an upper threshold of approximately 50% of the population. The fixed mechanism of transformation results in a fail-safe strategy for the population as half of the population generally keeps an intact copy of the original genome.

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Section: Introductionmentioning

confidence: 99%

Unbiased homeologous recombination during pneumococcal transformation allows for multiple chromosomal integration events

Kurushima

Campo

Raaphorst

et al. 2020

eLife

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“…Streptococcus pneumoniae is a leading cause of disease ranging from mild to severe manifestations. Invasive pneumococcal disease (IPD) includes the life-threatening conditions of bacteraemia and meningitis, both of which have high mortality rates [1,2] and S. pneumoniae is also a leading cause of pneumonia. A major virulence factor of S. pneumoniae is the polysaccharide capsule and, based on the biochemical properties of the capsule, S. pneumoniae is categorized into different serotypes.…”

Section: Introductionmentioning

confidence: 99%

“…A major virulence factor of S. pneumoniae is the polysaccharide capsule and, based on the biochemical properties of the capsule, S. pneumoniae is categorized into different serotypes. Currently, approximately 100 serotypes are known [2,3]. Several serotypes (including 7F, 14, 15B/C and 18C) have repeatedly been associated with invasive disease while other serotypes (such as 6B, 9 V, 19F and 23F) are more commonly associated with asymptomatic colonization of the human nasopharynx [1,[4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Pneumococcal serotype determines growth and capsule size in human cerebrospinal fluid

et al. 2020

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Background: The polysaccharide capsule is a major virulence factor of S. pneumoniae in diseases such as meningitis. While some capsular serotypes are more often found in invasive disease, high case fatality rates are associated with those serotypes more commonly found in asymptomatic colonization. We tested whether growth patterns and capsule size in human cerebrospinal fluid depends on serotype using a clinical isolate of S. pneumoniae and its capsule switch mutants. Results: We found that the growth pattern differed markedly from that in culture medium by lacking the exponential and lysis phases. Growth in human cerebrospinal fluid was reduced when strains lost their capsules. When a capsule was present, growth was serotype-specific: high carriage serotypes (6B, 9 V, 19F and 23F) grew better than low carriage serotypes (7F, 14, 15B/C and 18C). Growth correlated with the case-fatality rates of serotypes reported in the literature. Capsule size in human cerebrospinal fluid also depended on serotype. Conclusions: We propose that serotype-specific differences in disease severity observed in meningitis patients may, at least in part, be explained by differences in growth and capsule size in human cerebrospinal fluid. This information could be useful to guide future vaccine design.

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“…23-valent polysaccharide vaccine and polyvalent glycoconjugate vaccines) are based on the capsular polysaccharide. The introduction of pneumococcal vaccines has led to a decrease in the prevalence of vaccine serotypes (Croucher et al, 2018). The replacement of serotypes that are a part of current pneumococcal vaccines with nonvaccine serotypes has been reported (Ciruela et al, 2018;Sakata et al, 2018;Usuf et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Structural insights into the substrate specificity of SP_0149, the substrate-binding protein of a methionine ABC transporter from Streptococcus pneumoniae

et al. 2019

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Successful pathogenesis is a cumulative effect of the virulence factors of a pathogen and its capability to efficiently utilize the available nutrients from the host. Streptococcus pneumoniae, a Gram‐positive opportunistic pathogen, may either reside asymptomatically as a nasopharyngeal commensal inside the human host or cause lethal diseases, including pneumonia, meningitis and sepsis. S. pneumoniae is known to acquire methionine (Met) from its host through a Met importer. Here, the crystal structure of the substrate‐binding protein (SBP; SP_0149) of an ABC importer with Met bound is reported at a resolution of 1.95 Å. The three‐dimensional structure of SBP shows that it is composed of two distinct domains, each consisting of a mixed β‐sheet flanked by helices. The substrate, Met, is bound in the central part of the interface between the two domains. The overall structure of SP_0149 resembles those of SBPs from other reported bacterial Met and Gly‐Met dipeptide transporters. However, a detailed analysis of these structures shows notable variations in the amino‐acid composition of the substrate‐binding pockets of the SP_0149–Met and GmpC–Gly‐Met structures. In particular, SP_0149 harbors Thr212 and Tyr114, whereas the corresponding residues in GmpC are Gly and Val. This difference is likely to be the underlying basis for their differential substrate specificity. In summary, the structure of the SP_0149–Met complex provides insights into the transport function of SP_0149 and its interactions with methionine. It opens up avenues for the rational design of inhibitors of SP_0149 through a structure‐mediated approach.

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Pneumococcal Vaccines: Host Interactions, Population Dynamics, and Design Principles

Cited by 50 publications

References 200 publications

Unbiased homeologous recombination during pneumococcal transformation allows for multiple chromosomal integration events

Unbiased homeologous recombination during pneumococcal transformation allows for multiple chromosomal integration events

Pneumococcal serotype determines growth and capsule size in human cerebrospinal fluid

Structural insights into the substrate specificity of SP_0149, the substrate-binding protein of a methionine ABC transporter from Streptococcus pneumoniae

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