Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus pneumoniae isolates

Salter, Susannah J.; Hinds, Jason; Gould, Katherine A.; Lambertsen, Lotte; Hanage, William P.; Antonio, Martín; Turner, Paul; Hermans, Peter W. M.; Bootsma, Hester J.; O'Brien, Katherine L.; Bentley, Stephen D.

doi:10.1099/mic.0.056580-0

Cited by 72 publications

(82 citation statements)

References 47 publications

(55 reference statements)

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“…Genetic studies of cps loci from NT isolates revealed two broad NT groups (110,111). Group I NT isolates retain the characteristic genetic elements of the cps locus (112,113), while cps loci of group II NT isolates do not encode PS synthesis machinery but have genes for distinct proteins such as PspK (also identified as NspA) (100,111) and homologs of the putative peptide permease AliB (110,111). These proteins may facilitate epithelial adhesion and colonization, as almost all NT isolates from the NP belong to group II.…”

Section: Nontypeable Pneumococcimentioning

confidence: 99%

Pneumococcal Capsules and Their Types: Past, Present, and Future

et al. 2015

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SUMMARY Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.

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Section: Nontypeable Pneumococcimentioning

confidence: 99%

Pneumococcal Capsules and Their Types: Past, Present, and Future

et al. 2015

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“…If an increase in colonization occurs through the acquisition of pspK, this would allow NTSp strains that would normally be cleared to persist, increasing the possibility that they will cause disease and spread to other human hosts. The original NTSp isolates containing PspK were initially found in South Korea, but other isolates containing PspK have also been identified in Thailand and the Netherlands under the name nontypeable pneumococcal surface protein (nspA) (12,18). This may indicate either that PspK is naturally ubiquitous in NTSp isolates or that it has been rapidly disseminating in the population.…”

Section: Discussionmentioning

confidence: 99%

“…For NTSp strains to colonize as efficiently as encapsulated strains, there must be a compensatory mechanism, such as a surface protein like PspK (14,15). Pneumococcal surface proteins have been shown to increase colonization and mediate immune evasion, leading to the development of disease (16)(17)(18). Evidence for the importance of these proteins in NTSp colonization is currently lacking, but in nontypeable Haemophilus influenzae (NTHI), surface proteins have been shown to be important in nasopharyngeal adherence and colonization (19,20).…”

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PspK of Streptococcus pneumoniae Increases Adherence to Epithelial Cells and Enhances Nasopharyngeal Colonization

et al. 2013

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f Streptococcus pneumoniae (the pneumococcus) colonizes the human nasopharynx and can cause invasive disease aided by the pneumococcal capsule. Group II nontypeable S. pneumoniae (NTSp) lacks a polysaccharide capsule, and a subgroup of NTSp carriage isolates has been found to have a novel gene, pneumococcal surface protein K (pspK), which replaces the capsule locus. A recent rise in the number of NTSp isolates colonizing the human nasopharynx has been observed, but the colonization factors of NTSp have not been well studied. PspK has been shown to play a role in mouse colonization. We therefore examined PspKmediated immune evasion along with adherence to host cells and colonization. PspK bound human secretory immunoglobulin A (sIgA) but not the complement regulator factor H and did not decrease C3b deposition on the pneumococcal surface. PspK increased binding of pneumococci to epithelial cells and enhanced pneumococcal colonization independently of the genetic background. Understanding how NTSp colonizes and survives within the nasopharynx is important due to the increase in NTSp carriage. Our data suggest that PspK may aid in the persistence of NTSp within the nasopharynx but is not involved in invasion.

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“…Group I NT strains possess a cps locus very similar to that of encapsulated strains. Group II NT strains lack the vast majority of the cps locus and instead harbor other genes, such as pspK (encoding an LPXTG-anchored protein potentially involved in epithelial adhesion and invasion), nspA [encoding a novel surface protein which may interact with the human poly(Ig) receptor], and genes with significant sequence similarity to aliB, which encodes a pep-tide-binding molecule associated with an ABC transporter (19)(20)(21)(22)(23). While it is clear that the replacement of the entire cps locus results in an acapsular strain, the molecular mechanism(s) responsible for reduced/loss of capsule in conjunctival clinical isolates with a seemingly intact cps locus is incompletely understood.…”

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Mutations in Pneumococcal cpsE Generated via In Vitro Serial Passaging Reveal a Potential Mechanism of Reduced Encapsulation Utilized by a Conjunctival Isolate

et al. 2015

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The polysaccharide capsule of Streptococcus pneumoniae is required for nasopharyngeal colonization and for invasive disease in the lungs, blood, and meninges. In contrast, the vast majority of conjunctival isolates are acapsular. The first serotype-specific gene in the capsule operon, cpsE, encodes the initiating glycosyltransferase and is one of the few serotype-specific genes that can tolerate null mutations. This report characterizes a spontaneously arising TIGR4 mutant exhibiting a reduced capsule, caused by a 6-nucleotide duplication in cpsE which results in duplication of Ala and Ile at positions 45 and 46. This strain (AI45dup) possessed more exposed phosphorylcholine and was hypersusceptible to C3 complement deposition compared to the wild type. Accordingly, the mutant was significantly better at forming abiotic biofilms and binding epithelial cells in vitro but was avirulent in a sepsis model. In vitro serial passaging of the wild-type strain failed to reproduce the AI45dup mutation but instead led to a variety of mutants with reduced capsule harboring single nucleotide polymorphisms (SNPs) in cpsE. A single passage in the sepsis model after high-dose inoculation readily yielded revertants of AI45dup with restored wild-type capsule level, but the majority of SNP alleles of cpsE could not revert, suppress, or bypass. Analysis of cpsE in conjunctival isolates revealed a strain with a single missense mutation at amino acid position 377, which was responsible for reduced encapsulation. This study supports the hypothesis that spontaneous, nonreverting mutations in cpsE serve as a form of adaptive mutation by providing a selective advantage to S. pneumoniae in niches where expression of capsule is detrimental. IMPORTANCEWhile the capsule of Streptococcus pneumoniae is required for colonization and invasive disease, most conjunctival isolates are acapsular by virtue of deletion of the entire capsular operon. We show that spontaneous acapsular mutants isolated in vitro harbor mostly nonrevertible single nucleotide polymorphism (SNP) null mutations in cpsE, encoding the initiating glycosyltransferase. From a small collection of acapsular conjunctival isolates, we identified one strain with a complete capsular operon but containing a SNP in cpsE that we show is responsible for the acapsular phenotype. We propose that acapsular conjunctival isolates may arise initially from such nonreverting SNP null mutations in cpsE, which can be followed later by deletion of portions or all of the cps operon. Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium that is frequently found as a commensal organism of the human nasopharynx. However, depending on the site of dissemination, it can also cause various invasive diseases, including pneumonia, otitis media, sepsis, and meningitis (1-4). One critical pneumococcal virulence factor is the capsular polysaccharide (capsule), of which over 90 different serotypes have been characterized. The capsule has many important immune evasion functions, including...

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Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus pneumoniae isolates

Cited by 72 publications

References 47 publications

Pneumococcal Capsules and Their Types: Past, Present, and Future

Pneumococcal Capsules and Their Types: Past, Present, and Future

PspK of Streptococcus pneumoniae Increases Adherence to Epithelial Cells and Enhances Nasopharyngeal Colonization

Mutations in Pneumococcal cpsE Generated via In Vitro Serial Passaging Reveal a Potential Mechanism of Reduced Encapsulation Utilized by a Conjunctival Isolate

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