A two‐component signal‐transducing system is involved in competence and penicillin susceptibility in laboratory mutants of <i>Streptococcus pneumoniae</i>

Guenzi, Eric; Gasc, Anne-Marie; Sicard, Michel; Hakenbeck, Regine

doi:10.1111/j.1365-2958.1994.tb01038.x

Cited by 197 publications

(201 citation statements)

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“…StkP is involved during exponential growth (Authors to be added, unpublished data), and CiaRH is involved during stasis (Guenzy et al 1994). On the one hand, comparison of the kinetics of autolysis in cultures of strains carrying either the ciaRH or both the ciaRH and the luxS mutations, indicates an additive contribution of LuxS and CiaRH to cellular integrity during stasis (Fig.…”

Section: Impact Of Luxs On Vegetative Growthmentioning

confidence: 99%

“…LuxS regulation appears to be independent of the CSP, ComAB, ComDE regulatory network. The TCST system CiaRH is the major negative regulator of competence (Guenzy et al, 1994), and controls the cellular level of comCDE mRNA (Echenique et al, 2000). In a competence-derepressed ciaRH mutant strain, luxS mutation further increases the competence level and the time-window of expression, suggesting additive competence repression by LuxS and CiaRH.…”

Section: Competence Developmentmentioning

confidence: 99%

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LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

et al. 2006

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The ubiquitous protein LuxS with S-ribosylhomocysteinase activity is involved in S-adenosyl methionine detoxification, C-1 unit recycling and the production of autoinducers that allow the cell to sense and respond to cell density. Independent reports describe the impact of LuxS deficiency on Streptococcus pneumoniae virulence in the mouse. In vitro, LuxS deficiency confers discrete phenotypes. A combined approach using genetic dissection and mixed-culture experiments allowed the involvement of LuxS in the developmental physiology of S. pneumoniae to be investigated. Functional LuxS was found to be related on the one hand to down-regulation of competence, and on the other hand to attenuation of autolysis in cultures entering stationary phase. The competence phenotype of luxS mutant bacteria was complemented by media conditioned by competence-defective ComAB0 bacteria, but not by BSA. The autolytic phenotype was complemented by BSA, but not by conditioned supernatants. It is suggested that the impact of LuxS on competence, but not on autolysis, involves cell-cell communication. The phenotype of luxS mutant strains reveals a hierarchy in the competence regulatory networks of S. pneumoniae. INTRODUCTIONLuxS, the S-ribosylhomocysteinase involved in furanosyl borate diester, autoinducer 2 (AI-2) production from Sribosylhomocysteine, is ubiquitous in prokaryotes (Sun et al., 2004). Since its discovery (Bassler et al., 1997) and chemical characterization (Chen et al., 2002), the role of AI-2 in the regulation of light production, biofilm formation and virulence in response to high cell density (quorum sensing) has been elucidated in several Gram-negative bacteria, including Vibrio species (Surette et al., 1999;Miller et al., 2002;Hammer & Bassler, 2003;Henke & Bassler, 2004;Vendeville et al., 2005). In some species, furanone uptake and processing involving the lsrACDBFGE operon has been described Xavier & Bassler, 2005). Bioluminescence activation in Vibrio harveyi by conditioned media represents the test for AI-2 production by a given species and supports the paradigm of AI-2-mediated interspecies cell-cell communication culminating in genetic regulation Xavier & Bassler, 2003). Recent studies give credence to the involvement of LuxS in host-bacterial communication (Maroui & Sela, 2003;Sperandino et al., 2003). However, in Neisseria meningitis, AI-2 production is not related to the regulation of specific genes in vitro (Schauder et al., 2005;Dove et al., 2003). In Streptococcus pneumoniae, the impact of LuxS loss-offunction mutations on experimental virulence and genetic expression has been reported; however, results concerning production of AI-2, active in the 'vibrio test', by pneumococci, are divergent (Joyce et al. 2004;Stroeher et al., 2003). In order to get further insight into the function of LuxS in these Gram-positive bacteria, we have investigated its role in vitro on the developmental phenotypes classically observed: competence for genetic transformation during exponential growth, and autolysis when the cult...

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Section: Impact Of Luxs On Vegetative Growthmentioning

confidence: 99%

Section: Competence Developmentmentioning

confidence: 99%

LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

et al. 2006

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“…Columns 2 and 3 show the classification of HKs and RRs, respectively. The classification into HK and RR subfamilies was based on the classification described by Grebe & Stock (1999 (Guenzi et al, 1994;Mascher et al, 2003b;Throup et al, 2000). Because of their similarity with LisKR, ArlSR and CiaHR, it is conceivable that TCSs 24, 25 and 26 of the B. cereus group also play a role in virulence.…”

Section: Function Prediction: a Footprint Analysis Including B Subtilismentioning

confidence: 99%

Comparative analysis of two-component signal transduction systems of Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis

et al. 2006

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Members of the Bacillus cereus group are ubiquitously present in the environment and can adapt to a wide range of environmental fluctuations. In bacteria, these adaptive responses are generally mediated by two-component signal transduction systems (TCSs), which consist of a histidine kinase (HK) and its cognate response regulator (RR). With the use of in silico techniques, a complete set of HKs and RRs was recovered from eight completely sequenced B. cereus group genomes. By applying a bidirectional best-hits method combined with gene neighbourhood analysis, a footprint of these proteins was made. Around 40 HK-RR gene pairs were detected in each member of the B. cereus group. In addition, each member contained many HK and RR genes not encoded in pairs (‘orphans’). Classification of HKs and RRs based on their enzymic domains together with the analysis of two neighbour-joining trees of these domains revealed putative interaction partners for most of the ‘orphans’. Putative biological functions, including involvement in virulence and host–microbe interactions, were predicted for the B. cereus group HKs and RRs by comparing them with those of B. subtilis and other micro-organisms. Remarkably, B. anthracis appeared to lack specific HKs and RRs and was found to contain many truncated, putatively non-functional, HK and RR genes. It is hypothesized that specialization of B. anthracis as a pathogen could have reduced the range of environmental stimuli to which it is exposed. This may have rendered some of its TCSs obsolete, ultimately resulting in the deletion of some HK and RR genes.

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“…The best characterized of these is ComDE, which activates the genetic competence system in response to a competence-stimulating peptide (6,7). Another system, CiaRH, also affects competence and has been shown to control a novel virulence factor, HtrA (8,9). More recently, HK͞RR04 has been linked to the control of the Mn transporter PsaA, although this regulation was apparently strainspecific (10).…”

mentioning

confidence: 99%

The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae

Standish

Stroeher

Paton

2005

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

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Streptococcus pneumoniae encounters a number of environmental niches in the body, including the nasopharynx, lungs, blood, middle ear, and brain. Recent studies have identified 13 putative two-component signal-transduction systems in S. pneumoniae, which are likely to be important for gene regulation in response to external stimuli. Here, we present conclusive evidence for the regulation of choline binding protein A (CbpA), a major pneumococcal virulence factor and protective antigen, by one of these two-component signal-transduction systems. We have demonstrated divergent expression of cbpA in unmarked hk06 and rr06 deletion mutants relative to wild-type S. pneumoniae D39 by using Western immunoblotting and real-time RT-PCR. Electrophoretic mobility-shift and solid-phase binding assays have demonstrated the binding of RR06 to the promoter region of cbpA, suggesting that RR06͞HK06 directly regulates cbpA transcription. We have also shown that this system is important for the ability of the pneumococcus to adhere to epithelial cells in vitro and to survive and proliferate in an in vivo mouse model. Thus, the RR06͞HK06 system has a significant role in pathogenesis, both in colonization and invasive disease.adherence ͉ two-component system ͉ pneumococcus ͉ colonization T he major human pathogen Streptococcus pneumoniae is responsible for diseases, including pneumonia, sepsis, meningitis, and otitis media. During the course of an infection, the pneumococcus encounters a number of different environmental niches, including the nasopharynx, lungs, blood, and potentially the brain. Thus, the regulation of virulence factors in response to external stimuli may be a principal determinant of the success or failure of the infection. Recently, several virulence-associated genes of S. pneumoniae have been shown to be differentially expressed in varying in vitro and in vivo conditions, but the underlying mechanism is unknown (1, 2). Two-component signal-transduction systems (TCSTSs) control the expression of virulence factors in a wide range of bacterial species in response to external stimuli (reviewed in ref.3). The typical TCSTS consists of a His kinase (HK) and a response regulator (RR). The HK, usually present in the cell membrane, responds to external stimuli by autophosphorylating a conserved His residue, with subsequent transfer of this phosphate group to the RR. The resultant conformational change enables the RR to bind to the promoter region of target gene(s) and act as a transcription factor.The S. pneumoniae genome sequence contains 13 putative TCSTSs, along with one orphan RR (4, 5). The best characterized of these is ComDE, which activates the genetic competence system in response to a competence-stimulating peptide (6, 7). Another system, CiaRH, also affects competence and has been shown to control a novel virulence factor, HtrA (8, 9). More recently, HK͞RR04 has been linked to the control of the Mn transporter PsaA, although this regulation was apparently strainspecific (10). In this study, we used unmarked dele...

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A two‐component signal‐transducing system is involved in competence and penicillin susceptibility in laboratory mutants of Streptococcus pneumoniae

Cited by 197 publications

References 49 publications

LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

Comparative analysis of two-component signal transduction systems of Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis

The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae

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