The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jufang Wang - One of the best experts on this subject based on the ideXlab platform.
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salk salr a two Component Signal transduction system is essential for full virulence of highly invasive streptococcus suis serotype 2
PLOS ONE, 2008Co-Authors: Ming Li, Changjun Wang, Youjun Feng, Gong Cheng, Jing Wang, Junchao Ge, Feng Zheng, Yaqing Dong, Jufang Wang, Hongli DuAbstract:Background Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. Methodology/Principal Findings 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-Component Signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant ΔsalKR restored its soaring pathogenicity. Colonization experiments showed that the ΔsalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the ΔsalKR mutant. Conclusions/Significance These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.
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salk salr a two Component Signal transduction system is essential for full virulence of highly invasive streptococcus suis serotype 2
PLOS ONE, 2008Co-Authors: Changjun Wang, Youjun Feng, Gong Cheng, Jing Wang, Feng Zheng, Yaqing Dong, Xiuzhen Pan, Min Cao, Di Liu, Jufang WangAbstract:BACKGROUND Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-Component Signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant. CONCLUSIONS/SIGNIFICANCE These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.
David J Holmes - One of the best experts on this subject based on the ideXlab platform.
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inactivation of a two Component Signal transduction system saers eliminates adherence and attenuates virulence of staphylococcus aureus
Infection and Immunity, 2006Co-Authors: Xudong Liang, David J Holmes, Christina Landwehr, Chuanxin Yu, Yinduo JiAbstract:Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-Component Signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding α-, β-, and γ-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells.
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global regulation of gene expression by arlrs a two Component Signal transduction regulatory system of staphylococcus aureus
Journal of Bacteriology, 2005Co-Authors: Xudong Liang, David J Holmes, Li Zheng, Christina Landwehr, Dwayne Lunsford, Yinduo JiAbstract:Staphylococcus aureus expresses various cell wall-associated and extracellular virulence factors, coordinately controlled by different two-Component Signal transduction systems and transcriptional regulators. In this study, we used microarray technology to identify the genes regulated by ArlR. The microarray data indicate that ArlR functions as a positive regulator and also as a negative repressor to directly and/or indirectly mediate the expression of at least 114 genes involved in different functions, including autolysis, cell division, growth, and pathogenesis.
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a genomic analysis of two Component Signal transduction in streptococcus pneumoniae
Molecular Microbiology, 2002Co-Authors: John P Throup, Kristin K Koretke, Alexander P Bryant, Karen A Ingraham, Alison F Chalker, Yigong Ge, Andrea Marra, Nicola G Wallis, James R Brown, David J HolmesAbstract:Summary A genomics-based approach was used to identify the entire gene complement of putative two-Component Signal transduction systems (TCSTSs) in Streptococcus pneumoniae. A total of 14 open reading frames (ORFs) were identified as putative response regulators, 13 of which were adjacent to genes encoding probable histidine kinases. Both the histidine kinase and response regulator proteins were categorized into subfamilies on the basis of phylogeny. Through a systematic programme of mutagenesis, the importance of each novel TCSTS was determined with respect to viability and pathogenicity. One TCSTS was identified that was essential for the growth of S. pneumoniae. This locus was highly homologous to the yycFG gene pair encoding the essential response regulator/histidine kinase proteins identified in Bacillus subtilis and Staphylococcus aureus. Separate deletions of eight other loci led in each case to a dramatic attenuation of growth in a mouse respiratory tract infection model, suggesting that these Signal transduction systems are important for the in vivo adaptation and pathogenesis of S. pneumoniae. The identification of conserved TCSTSs important for both pathogenicity and viability in a Gram-positive pathogen highlights the potential of two-Component Signal transduction as a multiComponent target for antibacterial drug discovery.
Changjun Wang - One of the best experts on this subject based on the ideXlab platform.
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salk salr a two Component Signal transduction system is essential for full virulence of highly invasive streptococcus suis serotype 2
PLOS ONE, 2008Co-Authors: Ming Li, Changjun Wang, Youjun Feng, Gong Cheng, Jing Wang, Junchao Ge, Feng Zheng, Yaqing Dong, Jufang Wang, Hongli DuAbstract:Background Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. Methodology/Principal Findings 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-Component Signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant ΔsalKR restored its soaring pathogenicity. Colonization experiments showed that the ΔsalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the ΔsalKR mutant. Conclusions/Significance These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.
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salk salr a two Component Signal transduction system is essential for full virulence of highly invasive streptococcus suis serotype 2
PLOS ONE, 2008Co-Authors: Changjun Wang, Youjun Feng, Gong Cheng, Jing Wang, Feng Zheng, Yaqing Dong, Xiuzhen Pan, Min Cao, Di Liu, Jufang WangAbstract:BACKGROUND Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-Component Signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant. CONCLUSIONS/SIGNIFICANCE These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.
Michael T Laub - One of the best experts on this subject based on the ideXlab platform.
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determinants of specificity in two Component Signal transduction
Current Opinion in Microbiology, 2013Co-Authors: Anna I Podgornaia, Michael T LaubAbstract:Maintaining the faithful flow of information through Signal transduction pathways is critical to the survival and proliferation of organisms. This problem is particularly challenging as many Signaling proteins are part of large, paralogous families that are highly similar at the sequence and structural levels, increasing the risk of unwanted cross-talk. To detect environmental Signals and process information, bacteria rely heavily on two-Component Signaling systems comprised of sensor histidine kinases and their cognate response regulators. Although most species encode dozens of these Signaling pathways, there is relatively little cross-talk, indicating that individual pathways are well insulated and highly specific. Here, we review the molecular mechanisms that enforce this specificity. Further, we highlight recent studies that have revealed how these mechanisms evolve to accommodate the introduction of new pathways by gene duplication.
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evolution of two Component Signal transduction systems
Annual Review of Microbiology, 2012Co-Authors: Emily J Capra, Michael T LaubAbstract:To exist in a wide range of environmental niches, bacteria must sense and respond to a variety of external Signals. A primary means by which this occurs is through two-Component Signal transduction pathways, typically composed of a sensor histidine kinase that receives the input stimuli and then phosphorylates a response regulator that effects an appropriate change in cellular physiology. Histidine kinases and response regulators have an intrinsic modularity that separates Signal input, phosphotransfer, and output response; this modularity has allowed bacteria to dramatically expand and diversify their Signaling capabilities. Recent work has begun to reveal the molecular basis by which two-Component proteins evolve. How and why do orthologous Signaling proteins diverge? How do cells gain new pathways and recognize new Signals? What changes are needed to insulate a new pathway from existing pathways? What constraints are there on gene duplication and lateral gene transfer? Here, we review progress made in ...
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evolution of two Component Signal transduction systems
Annual Review of Microbiology, 2012Co-Authors: Emily J Capra, Michael T LaubAbstract:To exist in a wide range of environmental niches, bacteria must sense and respond to a variety of external Signals. A primary means by which this occurs is through two-Component Signal transduction pathways, typically composed of a sensor histidine kinase that receives the input stimuli and then phosphorylates a response regulator that effects an appropriate change in cellular physiology. Histidine kinases and response regulators have an intrinsic modularity that separates Signal input, phosphotransfer, and output response; this modularity has allowed bacteria to dramatically expand and diversify their Signaling capabilities. Recent work has begun to reveal the molecular basis by which two-Component proteins evolve. How and why do orthologous Signaling proteins diverge? How do cells gain new pathways and recognize new Signals? What changes are needed to insulate a new pathway from existing pathways? What constraints are there on gene duplication and lateral gene transfer? Here, we review progress made in answering these questions, highlighting how the integration of genome sequence data with experimental studies is providing major new insights.
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rewiring the specificity of two Component Signal transduction systems
Cell, 2008Co-Authors: Jeffrey M Skerker, Mark Goulian, Barrett S Perchuk, Albert Siryaporn, Emma A Lubin, Orr Ashenberg, Michael T LaubAbstract:SUMMARY Two-Component Signal transduction systems are the predominant means by which bacteria sense and respond to environmental stimuli. Bacteria often employ tens or hundreds of these paralogous Signalingsystems,comprisedofhistidinekinases(HKs)and their cognate response regulators (RRs). Faithful transmission of information through these Signaling pathways and avoidance of detrimental crosstalk demand exquisite specificity of HK-RR interactions. To identifythedeterminantsoftwo-ComponentSignaling specificity, we examined patterns of amino acid coevolution in large, multiple sequence alignments of cognate kinase-regulator pairs. Guided by these results, we demonstrate that a subset of the coevolving residues is sufficient, when mutated, to completely switch the substrate specificity of the kinase EnvZ. Our results shed light on the basis of molecular discrimination in two-Component Signaling pathways, provide a general approach for the rational rewiring of these pathways, and suggest that analyses of coevolutionmayfacilitatethereprogrammingofother Signaling systems and protein-protein interactions.
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specificity in two Component Signal transduction pathways
Annual Review of Genetics, 2007Co-Authors: Michael T Laub, Mark GoulianAbstract:Two-Component Signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions. In the prototypical two-Component system, a sensor histidine kinase catalyzes its autophosphorylation and then subseqeuntly transfers the phosphoryl group to a response regulator, which can then effect changes in cellular physiology, often by regulating gene expression. The utility of these Signaling systems is underscored by their prevalence throughout the bacterial kingdom and by the fact that many bacteria contain dozens, or sometimes hundreds, of these Signaling proteins. The presence of so many highly related Signaling proteins in individual cells creates both an opportunity and a challenge. Do cells take advantage of the similarity between Signaling proteins to integrate Signals or diversify responses, and thereby enhance their ability to process information? Conversely, how do cells prevent unwanted cross-talk and maintain the insulation of distin...
Hongli Du - One of the best experts on this subject based on the ideXlab platform.
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salk salr a two Component Signal transduction system is essential for full virulence of highly invasive streptococcus suis serotype 2
PLOS ONE, 2008Co-Authors: Ming Li, Changjun Wang, Youjun Feng, Gong Cheng, Jing Wang, Junchao Ge, Feng Zheng, Yaqing Dong, Jufang Wang, Hongli DuAbstract:Background Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. Methodology/Principal Findings 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-Component Signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant ΔsalKR restored its soaring pathogenicity. Colonization experiments showed that the ΔsalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the ΔsalKR mutant. Conclusions/Significance These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.