Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems
2020
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Details
- Autor(en) / Beteiligte
- Titel
- Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems
- Ist Teil von
- PLoS pathogens, 2020-03, Vol.16 (3), p.e1008417
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2020
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Streptococcus pneumoniae is well known for phase variation between opaque (O) and transparent (T) colonies within clonal populations. While the O variant is specialized in invasive infection (with a thicker capsule and higher resistance to host clearance), the T counterpart possesses a relatively thinner capsule and thereby higher airway adherence and colonization. Our previous study found that phase variation is caused by reversible switches of the "opaque ON-or-OFF" methylomes or methylation patterns of pneumococcal genome, which is dominantly driven by the PsrA-catalyzed inversions of the DNA methyltransferase hsdS genes. This study revealed that switch frequency between the O and T variants is regulated by five transcriptional response regulators (rr) of the two-component systems (TCSs). The mutants of rr06, rr08, rr09, rr11 and rr14 produced significantly fewer O and more T colonies. Further mutagenesis revealed that RR06, RR08, RR09 and RR11 enrich the O variant by modulating the directions of the PsrA-catalyzed inversion reactions. In contrast, the impact of RR14 (RitR) on phase variation is independent of PsrA. Consistently, SMRT sequencing uncovered significantly diminished "opaque ON" methylome in the mutants of rr06, rr08, rr09 and rr11 but not that of rr14. Lastly, the phosphorylated form of RR11 was shown to activate the transcription of comW and two sugar utilization systems that are necessary for maintenance of the "opaque ON" genotype and phenotype. This work has thus uncovered multiple novel mechanisms that balance pneumococcal epigenetic status and physiology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1008417Titel-ID: cdi_plos_journals_2390750269
- Format
- –
- Schlagworte
- Bacterial Proteins - genetics, Bacterial Proteins - metabolism, Biology and Life Sciences, Chemical reactions, Colonies, Colonization, Deoxyribonucleic acid, DNA, DNA Methylation, DNA methyltransferase, DNA Restriction-Modification Enzymes - genetics, DNA Restriction-Modification Enzymes - metabolism, DNA sequencing, DNA, Bacterial - genetics, DNA, Bacterial - metabolism, Epigenesis, Genetic, Epigenetic inheritance, Epigenetics, Gene Expression Regulation, Bacterial, Genes, Genetic research, Genome, Bacterial, Genomes, Genomics, Genotypes, Health aspects, Infection, Inversions, Methylation, Mutagenesis, Mutants, Mutation, Novels, Phase variations, Phenotypes, Physical Sciences, Physiological aspects, Pneumonia, Proteins, Regulators, Research and Analysis Methods, Signal transduction, Streptococcus infections, Streptococcus pneumoniae, Streptococcus pneumoniae - genetics, Streptococcus pneumoniae - metabolism, Switches, Transcription, Transferases