ArticlePLoS pathogens2020
Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Maximizing bacterial survival: integrating sense-and-respond and bet-hedging mechanisms.Trends in microbiology · 2025Review
- A clarifying perspective on bacterial pseudo-receiver domains.Journal of bacteriology · 2025Review
- Streptococcus pneumoniae synchronizes the states of cell wall peptidoglycan acetylation and genome methylation by programmed DNA inversions.PLoS pathogens · 2025Article
- Competence Regulation inCurrent medicinal chemistry · 2025Review
- The SpxA1-TenA toxin-antitoxin system regulates epigenetic variations of Streptococcus pneumoniae by targeting protein synthesis.PLoS pathogens · 2024Article
- A comprehensive analysis of pneumococcal two-component system regulatory networks.NAR genomics and bioinformatics · 2024Article
- Complete m6A and m4C methylomes for group B streptococcal clinical isolates CJB111, A909, COH1, and NEM316.Microbiology resource announcements · 2024Article
- SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence inFrontiers in microbiology · 2024Article
- Article
- Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions.Nature communications · 2023Article
- Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.Nucleic acids research · 2023Article
- Effects of Capsular Polysaccharide amount on Pneumococcal-Host interactions.PLoS pathogens · 2023Article
- Influence of Streptococcus pneumoniae Within-Strain Population Diversity on Virulence and Pathogenesis.Microbiology spectrum · 2023Article
- Capsule type defines the capability of Klebsiella pneumoniae in evading Kupffer cell capture in the liver.PLoS pathogens · 2022Article
- The bacterial tyrosine kinase system CpsBCD governs the length of capsule polymers.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression.Microorganisms · 2021Article
- Prevalence of phase variable epigenetic invertons among host-associated bacteria.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.