The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Olaf Schneewind - One of the best experts on this subject based on the ideXlab platform.
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sec secretion and sortase mediated anchoring of proteins in gram positive Bacteria
Biochimica et Biophysica Acta, 2014Co-Authors: Olaf Schneewind, Dominique MissiakasAbstract:Signal peptide-driven secretion of precursor proteins directs polypeptides across the plasma membrane of Bacteria. Two pathways, Sec- and SRP-dependent, converge at the SecYEG translocon to thread unfolded precursor proteins across the membrane, whereas folded preproteins are routed via the Tat secretion pathway. Gram-Positive Bacteria lack an outer membrane and are surrounded by a rigid layer of peptidoglycan. Interactions with their environment are mediated by proteins that are retained in the cell wall, often through covalent attachment to the peptidoglycan. In this review, we describe the mechanisms for both Sec-dependent secretion and sortase-dependent assembly of proteins in the envelope of Gram-Positive Bacteria. This article is part of a Special Issue entitled: Protein trafficking and secretion in Bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.
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Lipoteichoic Acids, Phosphate-Containing Polymers in the Envelope of Gram-Positive Bacteria
Journal of Bacteriology, 2014Co-Authors: Olaf Schneewind, Dominique MissiakasAbstract:Lipoteichoic acids (LTA) are polymers of alternating units of a polyhydroxy alkane, including glycerol and ribitol, and phosphoric acid, joined to form phosphodiester units that are found in the envelope of Gram-Positive Bacteria. Here we review four different types of LTA that can be distinguished on the basis of their chemical structure and describe recent advances in the biosynthesis pathway for type I LTA, d-alanylated polyglycerol-phosphate linked to di-glucosyl-diacylglycerol. The physiological functions of type I LTA are discussed in the context of inhibitors that block their synthesis and of mutants with discrete synthesis defects. Research on LTA structure and function represents a large frontier that has been investigated in only few Gram-Positive Bacteria.
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Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-Positive Bacteria
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Stefan Richter, Olaf Schneewind, Derek Elli, Antoni P. A. Hendrickx, Joseph A. Sorg, Dominique MissiakasAbstract:The current epidemic of infections caused by antibiotic-resistant Gram-Positive Bacteria requires the discovery of new drug targets and the development of new therapeutics. Lipoteichoic acid (LTA), a cell wall polymer of Gram-Positive Bacteria, consists of 1,3-polyglycerol-phosphate linked to glycolipid. LTA synthase (LtaS) polymerizes polyglycerol-phosphate from phosphatidylglycerol, a reaction that is essential for the growth of Gram-Positive Bacteria. We screened small molecule libraries for compounds inhibiting growth of Staphylococcus aureus but not of Gram-negative Bacteria. Compound 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] blocked phosphatidylglycerol binding to LtaS and inhibited LTA synthesis in S. aureus and in Escherichia coli expressing ltaS. Compound 1771 inhibited the growth of antibiotic-resistant Gram-Positive Bacteria and prolonged the survival of mice with lethal S. aureus challenge, validating LtaS as a target for the development of antibiotics.
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Protein secretion and surface display in Gram-Positive Bacteria
Philosophical Transactions of the Royal Society B, 2012Co-Authors: Olaf Schneewind, Dominique MissiakasAbstract:The cell wall peptidoglycan of Gram-Positive Bacteria functions as a surface organelle for the transport and assembly of proteins that interact with the environment, in particular, the tissues of an infected host. Signal peptide-bearing precursor proteins are secreted across the plasma membrane of Gram-Positive Bacteria. Some precursors carry C-terminal sorting signals with unique sequence motifs that are cleaved by sortase enzymes and linked to the cell wall peptidoglycan of vegetative forms or spores. The sorting signals of pilin precursors are cleaved by pilus-specific sortases, which generate covalent bonds between proteins leading to the assembly of fimbrial structures. Other precursors harbour surface (S)-layer homology domains (SLH), which fold into a three-pronged spindle structure and bind secondary cell wall polysaccharides, thereby associating with the surface of specific Gram-Positive microbes. Type VII secretion is a non-canonical secretion pathway for WXG100 family proteins in mycoBacteria. Gram-Positive Bacteria also secrete WXG100 proteins and carry unique genes that either contribute to discrete steps in secretion or represent distinctive substrates for protein transport reactions.
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Protein sorting to the cell wall envelope of Gram-Positive Bacteria.
Biochimica et biophysica acta, 2004Co-Authors: Hung Ton-that, Luciano A Marraffini, Olaf SchneewindAbstract:The covalent anchoring of surface proteins to the cell wall envelope of Gram-Positive Bacteria occurs by a universal mechanism requiring sortases, extracellular transpeptidases that are positioned in the plasma membrane. Surface protein precursors are first initiated into the secretory pathway of Gram-Positive Bacteria via N-terminal signal peptides. C-terminal sorting signals of surface proteins, bearing an LPXTG motif or other recognition sequences, provide for sortase-mediated cleavage and acyl enzyme formation, a thioester linkage between the active site cysteine residue of sortase and the C-terminal carboxyl group of cleaved surface proteins. During cell wall anchoring, sortase acyl enzymes are resolved by the nucleophilic attack of peptidoglycan substrates, resulting in amide bond formation between the C-terminal end of surface proteins and peptidoglycan cross-bridges within the Bacterial cell wall envelope. The genomes of Gram-Positive Bacteria encode multiple sortase genes. Recent evidence suggests that sortase enzymes catalyze protein anchoring reactions of multiple different substrate classes with different sorting signal motif sequences, protein linkage to unique cell wall anchor structures as well as protein polymerization leading to the formation of pili on the surface of Gram-Positive Bacteria.
Alexander R Horswill - One of the best experts on this subject based on the ideXlab platform.
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Biosynthesis of peptide signals in Gram-Positive Bacteria.
Advances in Applied Microbiology, 2010Co-Authors: Matthew Thoendel, Alexander R HorswillAbstract:Gram-Positive Bacteria coordinate social behavior by sensing the extracellular level of peptide signals. These signals are biosynthesized through divergent pathways and some possess unusual functional chemistry as a result of posttranslational modifications. In this chapter, the biosynthetic pathways of Bacillus intracellular signaling peptides, Enterococcus pheromones, Bacillus subtilis competence pheromones, and cyclic peptide signals from Staphylococcus and other Bacteria are covered. With the increasing prevalence of the cyclic peptide signals in diverse Gram-Positive Bacteria, a focus on this biosynthetic mechanism and variations on the theme are discussed. Due to the importance of peptide systems in pathogenesis, there is emerging interest in quorum-quenching approaches for therapeutic intervention. The quenching strategies that have successfully blocked signal biosynthesis are also covered. As peptide signaling systems continue to be discovered, there is a growing need to understand the details of these communication mechanisms. This information will provide insight on how Gram-Positives coordinate cellular events and aid strategies to target these pathways for infection treatments.
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Biosynthesis of peptide signals in Gram-Positive Bacteria.
Advances in applied microbiology, 2010Co-Authors: Matthew Thoendel, Alexander R HorswillAbstract:Gram-Positive Bacteria coordinate social behavior by sensing the extracellular level of peptide signals. These signals are biosynthesized through divergent pathways and some possess unusual functional chemistry as a result of posttranslational modifications. In this chapter, the biosynthetic pathways of Bacillus intracellular signaling peptides, Enterococcus pheromones, Bacillus subtilis competence pheromones, and cyclic peptide signals from Staphylococcus and other Bacteria are covered. With the increasing prevalence of the cyclic peptide signals in diverse Gram-Positive Bacteria, a focus on this biosynthetic mechanism and variations on the theme are discussed. Due to the importance of peptide systems in pathogenesis, there is emerging interest in quorum-quenching approaches for therapeutic intervention. The quenching strategies that have successfully blocked signal biosynthesis are also covered. As peptide signaling systems continue to be discovered, there is a growing need to understand the details of these communication mechanisms. This information will provide insight on how Gram-Positives coordinate cellular events and aid strategies to target these pathways for infection treatments. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Dominique Missiakas - One of the best experts on this subject based on the ideXlab platform.
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sec secretion and sortase mediated anchoring of proteins in gram positive Bacteria
Biochimica et Biophysica Acta, 2014Co-Authors: Olaf Schneewind, Dominique MissiakasAbstract:Signal peptide-driven secretion of precursor proteins directs polypeptides across the plasma membrane of Bacteria. Two pathways, Sec- and SRP-dependent, converge at the SecYEG translocon to thread unfolded precursor proteins across the membrane, whereas folded preproteins are routed via the Tat secretion pathway. Gram-Positive Bacteria lack an outer membrane and are surrounded by a rigid layer of peptidoglycan. Interactions with their environment are mediated by proteins that are retained in the cell wall, often through covalent attachment to the peptidoglycan. In this review, we describe the mechanisms for both Sec-dependent secretion and sortase-dependent assembly of proteins in the envelope of Gram-Positive Bacteria. This article is part of a Special Issue entitled: Protein trafficking and secretion in Bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.
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Lipoteichoic Acids, Phosphate-Containing Polymers in the Envelope of Gram-Positive Bacteria
Journal of Bacteriology, 2014Co-Authors: Olaf Schneewind, Dominique MissiakasAbstract:Lipoteichoic acids (LTA) are polymers of alternating units of a polyhydroxy alkane, including glycerol and ribitol, and phosphoric acid, joined to form phosphodiester units that are found in the envelope of Gram-Positive Bacteria. Here we review four different types of LTA that can be distinguished on the basis of their chemical structure and describe recent advances in the biosynthesis pathway for type I LTA, d-alanylated polyglycerol-phosphate linked to di-glucosyl-diacylglycerol. The physiological functions of type I LTA are discussed in the context of inhibitors that block their synthesis and of mutants with discrete synthesis defects. Research on LTA structure and function represents a large frontier that has been investigated in only few Gram-Positive Bacteria.
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Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-Positive Bacteria
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Stefan Richter, Olaf Schneewind, Derek Elli, Antoni P. A. Hendrickx, Joseph A. Sorg, Dominique MissiakasAbstract:The current epidemic of infections caused by antibiotic-resistant Gram-Positive Bacteria requires the discovery of new drug targets and the development of new therapeutics. Lipoteichoic acid (LTA), a cell wall polymer of Gram-Positive Bacteria, consists of 1,3-polyglycerol-phosphate linked to glycolipid. LTA synthase (LtaS) polymerizes polyglycerol-phosphate from phosphatidylglycerol, a reaction that is essential for the growth of Gram-Positive Bacteria. We screened small molecule libraries for compounds inhibiting growth of Staphylococcus aureus but not of Gram-negative Bacteria. Compound 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] blocked phosphatidylglycerol binding to LtaS and inhibited LTA synthesis in S. aureus and in Escherichia coli expressing ltaS. Compound 1771 inhibited the growth of antibiotic-resistant Gram-Positive Bacteria and prolonged the survival of mice with lethal S. aureus challenge, validating LtaS as a target for the development of antibiotics.
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Protein secretion and surface display in Gram-Positive Bacteria
Philosophical Transactions of the Royal Society B, 2012Co-Authors: Olaf Schneewind, Dominique MissiakasAbstract:The cell wall peptidoglycan of Gram-Positive Bacteria functions as a surface organelle for the transport and assembly of proteins that interact with the environment, in particular, the tissues of an infected host. Signal peptide-bearing precursor proteins are secreted across the plasma membrane of Gram-Positive Bacteria. Some precursors carry C-terminal sorting signals with unique sequence motifs that are cleaved by sortase enzymes and linked to the cell wall peptidoglycan of vegetative forms or spores. The sorting signals of pilin precursors are cleaved by pilus-specific sortases, which generate covalent bonds between proteins leading to the assembly of fimbrial structures. Other precursors harbour surface (S)-layer homology domains (SLH), which fold into a three-pronged spindle structure and bind secondary cell wall polysaccharides, thereby associating with the surface of specific Gram-Positive microbes. Type VII secretion is a non-canonical secretion pathway for WXG100 family proteins in mycoBacteria. Gram-Positive Bacteria also secrete WXG100 proteins and carry unique genes that either contribute to discrete steps in secretion or represent distinctive substrates for protein transport reactions.
Matthew Thoendel - One of the best experts on this subject based on the ideXlab platform.
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Biosynthesis of peptide signals in Gram-Positive Bacteria.
Advances in Applied Microbiology, 2010Co-Authors: Matthew Thoendel, Alexander R HorswillAbstract:Gram-Positive Bacteria coordinate social behavior by sensing the extracellular level of peptide signals. These signals are biosynthesized through divergent pathways and some possess unusual functional chemistry as a result of posttranslational modifications. In this chapter, the biosynthetic pathways of Bacillus intracellular signaling peptides, Enterococcus pheromones, Bacillus subtilis competence pheromones, and cyclic peptide signals from Staphylococcus and other Bacteria are covered. With the increasing prevalence of the cyclic peptide signals in diverse Gram-Positive Bacteria, a focus on this biosynthetic mechanism and variations on the theme are discussed. Due to the importance of peptide systems in pathogenesis, there is emerging interest in quorum-quenching approaches for therapeutic intervention. The quenching strategies that have successfully blocked signal biosynthesis are also covered. As peptide signaling systems continue to be discovered, there is a growing need to understand the details of these communication mechanisms. This information will provide insight on how Gram-Positives coordinate cellular events and aid strategies to target these pathways for infection treatments.
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Biosynthesis of peptide signals in Gram-Positive Bacteria.
Advances in applied microbiology, 2010Co-Authors: Matthew Thoendel, Alexander R HorswillAbstract:Gram-Positive Bacteria coordinate social behavior by sensing the extracellular level of peptide signals. These signals are biosynthesized through divergent pathways and some possess unusual functional chemistry as a result of posttranslational modifications. In this chapter, the biosynthetic pathways of Bacillus intracellular signaling peptides, Enterococcus pheromones, Bacillus subtilis competence pheromones, and cyclic peptide signals from Staphylococcus and other Bacteria are covered. With the increasing prevalence of the cyclic peptide signals in diverse Gram-Positive Bacteria, a focus on this biosynthetic mechanism and variations on the theme are discussed. Due to the importance of peptide systems in pathogenesis, there is emerging interest in quorum-quenching approaches for therapeutic intervention. The quenching strategies that have successfully blocked signal biosynthesis are also covered. As peptide signaling systems continue to be discovered, there is a growing need to understand the details of these communication mechanisms. This information will provide insight on how Gram-Positives coordinate cellular events and aid strategies to target these pathways for infection treatments. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Richard P. Novick - One of the best experts on this subject based on the ideXlab platform.
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Peptide signaling in Staphylococcus aureusand other Gram-Positive Bacteria
2020Co-Authors: Gholson J. Lyon, Richard P. NovickAbstract:There are two basic types of Bacterial communication systems—those in which the signal is directed solely at other organisms and those in which the signal is sensed by the producing organism as well. The former are involved primarily in conjugation; the latter in adaptation to the environment. Gram-Positive Bacteria use small peptides for both types of signaling, whereas Gram-negative Bacteria use homoserine lactones. Since adaptation signals are autoinducers the response is population-density-dependent and has been referred to as “quorum-sensing”. Gram-negative Bacteria internalize the signals which act upon an intracellular receptor, whereas Gram-Positive Bacteria use them as ligands for the extracellular receptor of a two-component signaling module. In both cases, the signal activates a complex adaptation response involving many genes.
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Peptide signaling in Staphylococcus aureus and other Gram-Positive Bacteria.
Peptides, 2004Co-Authors: Gholson J. Lyon, Richard P. NovickAbstract:Abstract There are two basic types of Bacterial communication systems—those in which the signal is directed solely at other organisms and those in which the signal is sensed by the producing organism as well. The former are involved primarily in conjugation; the latter in adaptation to the environment. Gram-Positive Bacteria use small peptides for both types of signaling, whereas Gram-negative Bacteria use homoserine lactones. Since adaptation signals are autoinducers the response is population-density-dependent and has been referred to as “quorum-sensing”. Gram-negative Bacteria internalize the signals which act upon an intracellular receptor, whereas Gram-Positive Bacteria use them as ligands for the extracellular receptor of a two-component signaling module. In both cases, the signal activates a complex adaptation response involving many genes.
