An Epigenetic Switch Mediates Bistable Expression of the Type 1 Pilus Genes in Streptococcus pneumoniae

Basset, A; Turner, Keith H.; Boush, Elizabeth; Sayeed, Sabina; Dove, Simon L.; Malley, Richard

doi:10.1128/jb.06078-11

Cited by 24 publications

(15 citation statements)

References 20 publications

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“…The details of previous attempts were not fully described, but we hypothesized that the inability to generate a dpr mutant may have been because of potential polar effects on the expression levels of downstream essential genes. To test the hypothesis that dpr is part of an operon, RNA was purified from pneumococcal strains TIGR4 and 603 (a serotype 6B clinical isolate) (28,33). cDNA was generated using reverse transcriptase and used as the template to amplify PCR products covering the dpr-dhfr, dhfr-clpX, and dpr-clpX regions.…”

Section: Resultsmentioning

confidence: 99%

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

et al. 2014

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bStreptococcus pneumoniae (pneumococcus) produces hydrogen peroxide as a by-product of metabolism and provides a competitive advantage against cocolonizing bacteria. As pneumococci do not produce catalase or an inducible regulator of hydrogen peroxide, the mechanism of resistance to hydrogen peroxide is unclear. A gene responsible for resistance to hydrogen peroxide and iron in other streptococci is that encoding nonheme iron-containing ferritin, dpr, but previous attempts to study this gene in pneumococcus by generating a dpr mutant were unsuccessful. In the current study, we found that dpr is in an operon with the downstream genes dhfr and clpX. We generated a dpr deletion mutant which displayed normal early-log-phase and mid-logphase growth in bacteriologic medium but survived less well at stationary phase; the addition of catalase partially rescued the growth defect. We showed that the dpr mutant is significantly more sensitive to pH, heat, iron concentration, and oxidative stress due to hydrogen peroxide. Using a mouse model of colonization, we also showed that the dpr mutant displays a reduced ability to colonize and is more rapidly cleared from the nasopharynx. Our results thus suggest that Dpr is important for pneumococcal resistance to stress and for nasopharyngeal colonization.

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Section: Resultsmentioning

confidence: 99%

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

et al. 2014

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“…Depending on the exact characteristics, such systems may result in the occasional switching between alternative heritable phenotypes [46]. A positive feedback loop was recently found to mediate bistability in the expression of a virulence factor in S. pneumoniae [48]. A similar phenomenon seems likely in GAS.…”

Section: An Epigenetic Mechanism For Virulence Bistabilitymentioning

confidence: 99%

To harm or not to harm? On the evolution and expression of virulence in group A streptococci

Waldetoft

Råberg

2014

Trends in Microbiology

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“…Reports of bistable processes in S. pneumoniae and closely related bacteria include at least phase variation (132), persistence (91), competence (30,41), and the expression of type I pilus genes (11), with most of the repertoire of genes participating in these processes also being involved in virulence. An interesting example was provided by a global analysis of transcription during the onset of competence in pneumococci.…”

Section: Bistabilitymentioning

confidence: 99%

Toxin-Antitoxin Genes of the Gram-Positive Pathogen Streptococcus pneumoniae: So Few and Yet So Many

Chan

Moreno-Córdoba

Yeo

et al. 2012

Microbiol Mol Biol Rev

127

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SUMMARYPneumococcal infections cause up to 2 million deaths annually and raise a large economic burden and thus constitute an important threat to mankind. Because of the increase in the antibiotic resistance ofStreptococcus pneumoniaeclinical isolates, there is an urgent need to find new antimicrobial approaches to triumph over pneumococcal infections. Toxin-antitoxin (TA) systems (TAS), which are present in most living bacteria but not in eukaryotes, have been proposed as an effective strategy to combat bacterial infections. Type II TAS comprise a stable toxin and a labile antitoxin that form an innocuous TA complex under normal conditions. Under stress conditions, TA synthesis will be triggered, resulting in the degradation of the labile antitoxin and the release of the toxin protein, which would poison the host cells. The three functional chromosomal TAS fromS. pneumoniaethat have been studied as well as their molecular characteristics are discussed in detail in this review. Furthermore, a meticulous bioinformatics search has been performed for 48 pneumococcal genomes that are found in public databases, and more putative TAS, homologous to well-characterized ones, have been revealed. Strikingly, several unusual putative TAS, in terms of components and genetic organizations previously not envisaged, have been discovered and are further discussed. Previously, we reported a novel finding in which a unique pneumococcal DNA signature, the BOX element, affected the regulation of the pneumococcalyefM-yoeBTAS. This BOX element has also been found in some of the other pneumococcal TAS. In this review, we also discuss possible relationships between some of the pneumococcal TAS with pathogenicity, competence, biofilm formation, persistence, and an interesting phenomenon called bistability.

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An Epigenetic Switch Mediates Bistable Expression of the Type 1 Pilus Genes in Streptococcus pneumoniae

Cited by 24 publications

References 20 publications

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

To harm or not to harm? On the evolution and expression of virulence in group A streptococci

Toxin-Antitoxin Genes of the Gram-Positive Pathogen Streptococcus pneumoniae: So Few and Yet So Many

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