Deep genome annotation of the opportunistic human pathogen<i>Streptococcus pneumoniae</i>D39

Slager, Jelle; Aprianto, Rieza; Veening, Jan‐Willem

doi:10.1101/283663

Cited by 2 publications

(2 citation statements)

References 86 publications

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“…We then divided transmissions per cluster by the time to most recent common ancestor to obtain a rough estimate of transmissibility. We then used pyseer (Lees et al, 2018) to associate SNP variation mapped against the D39V reference (Slager et al, 2018) with this phenotype, while adjusting for population structure.…”

Section: Genomic Variations and Spn Transmissibilitymentioning

confidence: 99%

BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

Aggarwal

Lees

Jacobs

et al. 2022

Preprint

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Chromosomal barcoding and high-throughput sequencing were used to investigate the population dynamics of Streptococcus pneumoniae. During infant mouse colonization, >35-fold reduction in diversity and expansion of a single clonal lineage was observed within 1 day post-inoculation. This loss of diversity was not due to immune factors, host microbiota or exclusively because of genetic drift. Rather, it required the expression of blp bacteriocins induced by the BlpC-quorum sensing pheromone. This points towards the role of intra-strain competition whereby the subpopulation reaching a quorum eliminates others that have yet to activate the blp locus. We show that this loss of diversity also restricts the number of unique clones that could establish colonization during transmission between hosts. Moreover, we show that genetic variation in the blp locus is associated with transmissibility in the human population. We posit this is due to its importance in clonal selection and its role as a selfish element.

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Section: Genomic Variations and Spn Transmissibilitymentioning

confidence: 99%

BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

Aggarwal

Lees

Jacobs

et al. 2022

Preprint

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“…The pynA gene is predicted to be the first gene in a putative two-gene operon (PneumoBrowse; [10]), followed by a downstream gene cluster encoding proteins with different functions (spr1055 to spr1047) (Fig. 1B).…”

Section: Protein Conservation and Genomic Contextmentioning

confidence: 99%

PynA is a pyrimidine 5′‐nucleotidase that functions as an antimutator protein inStreptococcus pneumoniae

et al. 2019

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Streptococcus pneumoniae is a Gram‐positive bacterium that is a major agent of community‐acquired bacterial pneumonia, meningitis and sepsis. Although the mismatch repair function of S. pneumoniae has been assigned to the hexA‐hexB gene products, an enzyme capable of the direct elimination of noncanonical nucleotides from the cytoplasm has not been described for this bacterium. Our results show that Spr1057, a protein with previously unknown function, is involved in the inactivation of mutagenic pyrimidine nucleotides and was accordingly designated PynA (pyrimidine nucleotidase A). Biochemical assays confirmed the phosphatase activity of the recombinant enzyme and revealed its metal ion dependence for optimal enzyme activity. We demonstrated that PynA forms a homodimer with higher in vitro activity towards noncanonical 5‐fluoro‐2′‐deoxyuridine monophosphate than towards canonical thymidine monophosphate. Furthermore, we showed via in vivo assays that PynA protects cells against noncanonical pyrimidine derivatives such as 5‐fluoro‐2′‐deoxyuridine and prevents the incorporation of the potentially mutagenic 5‐bromo‐2′‐deoxyuridine (5‐BrdU) into DNA. Fluctuation analysis performed under S. pneumoniae exposure to 5‐BrdU revealed that the pynA null strain accumulates random mutations with high frequency, resulting in a 30‐fold increase in the mutation rate. The data support a model in which PynA, a protein conserved in other Gram‐positive bacteria, functions as a house‐cleaning enzyme by selectively eliminating noncanonical nucleotides and maintaining the purity of dNTP pools, similar to the YjjG protein described for Escherichia coli.

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Deep genome annotation of the opportunistic human pathogenStreptococcus pneumoniaeD39

Cited by 2 publications

References 86 publications

BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

PynA is a pyrimidine 5′‐nucleotidase that functions as an antimutator protein inStreptococcus pneumoniae

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