Characterization of a Two-component System in Streptococcus pyogenes Which Is Involved in Regulation of Hyaluronic Acid Production

Bernish, Brian W.; Rijn, I van de

doi:10.1074/jbc.274.8.4786

Cited by 99 publications

(99 citation statements)

References 38 publications

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“…Two-component systems in E. coli such as Ntr, Pho, and Che are capable of using AcP as a phosphate donor for their cognate regulation proteins (17). Many other bacteria are known to possess similar two-component systems, which can be modified to respond to AcP (30,31). This situation suggests that the strategy used in the artificial cell-cell communication system can be universally applied to other bacteria.…”

Section: Discussionmentioning

confidence: 96%

Design of artificial cell–cell communication using gene and metabolic networks

Bülter

Lee²,

Wong³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

152

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Artificial transcriptional networks have been used to achieve novel, nonnative behavior in bacteria. Typically, these artificial circuits are isolated from cellular metabolism and are designed to function without intercellular communication. To attain concerted biological behavior in a population, synchronization through intercellular communication is highly desirable. Here we demonstrate the design and construction of a gene-metabolic circuit that uses a common metabolite to achieve tunable artificial cell-cell communication. This circuit uses a threshold concentration of acetate to induce gene expression by acetate kinase and part of the nitrogen-regulation two-component system. As one application of the cell-cell communication circuit we created an artificial quorum sensor. Engineering of carbon metabolism in Escherichia coli made acetate secretion proportional to cell density and independent of oxygen availability. In these cells the circuit induced gene expression in response to a threshold cell density. This threshold can be tuned effectively by controlling ⌬pH over the cell membrane, which determines the partition of acetate between medium and cells. Mutagenesis of the enhancer sequence of the glnAp 2 promoter produced variants of the circuit with changed sensitivity demonstrating tunability of the circuit by engineering of its components. The behavior of the circuit shows remarkable predictability based on a mathematical design model.

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Section: Discussionmentioning

confidence: 96%

Design of artificial cell–cell communication using gene and metabolic networks

Bülter

Lee²,

Wong³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

152

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show abstract

“…In addition, csrRS mutants express increased amounts of csrRS mRNA, suggesting autoregulation (¢gure 3). Puri¢ed CsrR binds to the promoters of hasA, sagA, and speB, but only upon phosphorylation, which may be e¡ected presumably by CsrS in vivo but can be done using acyl phosphate in vitro (Bernish & Van de Rijn 1999;A. Miller, N. C. Engleberg and V. J. DiRita, unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Virulence gene regulation inside and outside

DiRita

Engleberg²,

Heath³

et al. 2000

Phil. Trans. R. Soc. Lond. B

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Much knowledge about microbial gene regulation and virulence is derived from genetic and biochemical studies done outside of hosts. The aim of this review is to correlate observations made in vitro and in vivo with two di¡erent bacterial pathogens in which the nature of regulated gene expression leading to virulence is quite di¡erent. The ¢rst is Vibrio cholerae, in which the concerted action of a complicated regulatory cascade involving several transcription activators leads ultimately to expression of cholera toxin and the toxin-coregulated pilus. The regulatory cascade is active in vivo and is also required for maintenance of V. cholerae in the intestinal tract during experimental infection. Nevertheless, speci¢c signals predicted to be generated in vivo, such as bile and a temperature of 37 8C, have a severe downmodulating e¡ect on activation of toxin and pilus expression. Another unusual aspect of gene regulation in this system is the role played by inner membrane proteins that activate transcription. Although the topology of these proteins suggests an appealing model for signal transduction leading to virulence gene expression, experimental evidence suggests that such a model may be simplistic. In Streptococcus pyogenes, capsule production is critical for virulence in an animal model of necrotizing skin infection. Yet capsule is apparently produced to high levels only from mutation in a two-component regulatory system, CsrR and CsrS. Thus it seems that in V. cholerae a complex regulatory pathway has evolved to control virulence by induction of gene expression in vivo, whereas in S. pyogenes at least one mode of pathogenicity is potentiated by the absence of regulation.

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“…The changes in transcript abundance following 4.5S RNA mutation are the reverse of that observed following mutation of covS (control of virulence Sensor; also known as csrS), which encodes the membrane-spanning sensor kinase component of the CovR/S two-component system (Bernish & van de Rijn, 1999;Engleberg et al, 2001;Federle et al, 1999;Gryllos et al, 2008;Levin & Wessels, 1998;Trevino et al, 2009). To test whether the transcriptional changes that occur following 4.5S RNA mutation are dependent on a functional covS gene we created a covS/4.5S RNA double mutant strain and compared transcript levels relative to a covS single mutant strain (Fig.…”

Section: The 45s Rna In Streptococcus Pyogenesmentioning

confidence: 99%

The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence

2010

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The signal recognition particle (SRP) is a ribonucleoprotein complex that targets proteins for secretion in a co-translational manner. While originally thought to be essential in all bacteria, recent data show that the SRP is dispensable in at least some streptococcal species. The SRP from the human pathogen group A Streptococcus (GAS, Streptococcus pyogenes) is predicted to be composed of protein Ffh and 4.5S RNA. Deletion of ffh alters the secretion of several GAS proteins, and leads to a severe reduction in virulence. Here, we report that mutation of the gene encoding 4.5S RNA results in phenotypes both similar to and distinct from that observed following ffh mutation. Similarities include a reduction in secretion of the haemolysin streptolysin O, and attenuation of virulence as assessed by a murine soft tissue infection model. Differences include a reduction in transcript levels for the genes encoding streptolysin O and NADglycohydrolase, and the reduced secretion of the SpeB protease. Several differences in transcript abundance between the parental and mutant strain were shown to be dependent on the sensorkinase-encoding gene covS. Using growth in human saliva as an ex vivo model of upper respiratory tract infection we identified that 4.5S RNA mutation leads to a 10-fold reduction in colony-forming units over time, consistent with the 4.5S RNA contributing to GAS growth and persistence during upper respiratory tract infections. Finally, we determined that the 4.5S RNA was essential for GAS to cause lethal infections in a murine bacteraemia model of infection. The data presented extend our knowledge of the contribution of the SRP to the virulence of an important Gram-positive pathogen.

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Characterization of a Two-component System in Streptococcus pyogenes Which Is Involved in Regulation of Hyaluronic Acid Production

Cited by 99 publications

References 38 publications

Design of artificial cell–cell communication using gene and metabolic networks

Design of artificial cell–cell communication using gene and metabolic networks

Virulence gene regulation inside and outside

The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence

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