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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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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, Derek Elli, Antoni P. A. Hendrickx, Joseph A. Sorg, Olaf Schneewind, 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.
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proteolytic cleavage and cell wall anchoring at the lpxtg motif of surface proteins in gram Positive Bacteria
Molecular Microbiology, 1994Co-Authors: William Wiley Navarre, Olaf SchneewindAbstract:Many surface proteins are thought to be anchored to the cell wall of Gram-Positive Bacteria via their C-terminus. Cell wall anchoring requires a specific sorting signal, normally located at the predicted C-terminus of surface proteins. Here we show that when placed into the middle of a polypeptide chain, the sorting signal causes the specific cleavage of the precursor as well as the cell wall anchoring of its N-terminal fragment, while the C-terminal fragment remains within the cytoplasm. N-terminal sequencing of the C-terminal cleavage fragment suggests that the cleavage site is located between threonine (T) and glycine (G) of the LPXTG motif, the signature sequence of cell wall sorting signals. All surface proteins harbouring an LPXTG sequence motif may therefore be cleaved and anchored by a universal mechanism. We also propose a novel hypothesis for the cell wall linkage of surface proteins in Gram-Positive Bacteria.
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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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, Derek Elli, Antoni P. A. Hendrickx, Joseph A. Sorg, Olaf Schneewind, 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.
Marc Lemaire - One of the best experts on this subject based on the ideXlab platform.
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Dodecyl sorbitan ethers as antimicrobials against Gram-Positive Bacteria
Bioorganic & Medicinal Chemistry Letters, 2017Co-Authors: Dorine Belmessieri, Charlotte Gozlan, Nicolas Duguet, Marie-christine Duclos, Gérard Lina, Andreas Redl, Oana Dumitrescu, Marc LemaireAbstract:Abstract A range of amphiphilic sorbitan ethers has been synthesized in two steps from sorbitan following an acetalization/hydrogenolysis sequence. These sorbitan ethers and the acetal intermediates have been evaluated as antimicrobials against Gram-negative and Gram-Positive Bacteria. No antimicrobial activity was observed for Gram-negative Bacteria. However, the compounds bearing a linear dodecyl chain exhibit antimicrobial activity (MIC as low as 8 μg/mL) against Gram-Positive Bacteria such as Listeria monocytogenes, Enterococcus faecalis and Staphylococcus aureus. Encouraged by these preliminary results, dodecyl sorbitan was tested against a range of resistant strains and was found to be active against vancomycin-, methicillin- and daptomycin-resistant strains (MIC = 32–64 μg/mL).
Koichi Kuwano - One of the best experts on this subject based on the ideXlab platform.
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novel Bacterial lipoprotein structures conserved in low gc content gram Positive Bacteria are recognized by toll like receptor 2
Journal of Biological Chemistry, 2012Co-Authors: Kenji Kurokawa, Kyounghwa Ryu, Rie Ichikawa, Akiko Masuda, Minsu Kim, Hanna Lee, Junho Chae, Takashi Shimizu, Tatsuya Saitoh, Koichi KuwanoAbstract:Bacterial lipoproteins/lipopeptides inducing host innate immune responses are sensed by mammalian Toll-like receptor 2 (TLR2). These Bacterial lipoproteins are structurally divided into two groups, diacylated or triacylated lipoproteins, by the absence or presence of an amide-linked fatty acid. The presence of diacylated lipoproteins has been predicted in low-GC content Gram-Positive Bacteria and mycoplasmas based on the absence of one modification enzyme in their genomes; however, we recently determined triacylated structures in low-GC Gram-Positive Staphylococcus aureus, raising questions about the actual lipoprotein structure in other low-GC content Gram-Positive Bacteria. Here, through intensive MS analyses, we identified a novel and unique Bacterial lipoprotein structure containing an N-acyl-S-monoacyl-glyceryl-cysteine (named the lyso structure) from low-GC Gram-Positive Enterococcus faecalis, Bacillus cereus, Streptococcus sanguinis, and Lactobacillus bulgaricus. Two of the purified native lyso-form lipoproteins induced proinflammatory cytokine production from mice macrophages in a TLR2-dependent and TLR1-independent manner but with a different dependence on TLR6. Additionally, two other new lipoprotein structures were identified. One is the “N-acetyl” lipoprotein structure containing N-acetyl-S-diacyl-glyceryl-cysteine, which was found in five Gram-Positive Bacteria, including Bacillus subtilis. The N-acetyl lipoproteins induced the proinflammatory cytokines through the TLR2/6 heterodimer. The other was identified in a mycoplasma strain and is an unusual diacyl lipoprotein structure containing two amino acids before the lipid-modified cysteine residue. Taken together, our results suggest the existence of novel TLR2-stimulating lyso and N-acetyl forms of lipoproteins that are conserved in low-GC content Gram-Positive Bacteria and provide clear evidence for the presence of yet to be identified key enzymes involved in the Bacterial lipoprotein biosynthesis.
Wolfgang Ludwig - One of the best experts on this subject based on the ideXlab platform.
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specific oligonucleotide probes for in situ detection of a major group of gram Positive Bacteria with low dna g c content
Systematic and Applied Microbiology, 1999Co-Authors: Harald Meier, Wolfgang Ludwig, Rudolf Amann, Karlheinz SchleiferAbstract:Summary Almost one thousand 16S rRNA sequences of Gram-Positive Bacteria with a low DNA G+C content from public databases were analyzed using the ARB software package. A signature region was identified between positions 354 and 371 ( E. coli numbering) for the Bacillus sub-branch of the Gram-Positive Bacteria with a low DNA G+C content, the former orders Bacillales and Lactobacillales . Three oligonucleotide probes, namely LGC354A, LGC354B, and LGC354C, were designed to target this diagnostic site. Their fluorescent derivatives were suitable for whole cell detection by fluorescence in situ hybridization (FISH). Hybridization conditions were adjusted for differentiation of target and related non-target reference species. When applying FISH to whole Bacterial cells in a sample of activated sludge from a communal wastewater treatment plant, members of the Bacillus sub-branch were detected at levels from 0.01% of cells in samples fixed with paraformaldehyde to over 8 percent in the same samples fixed with ethanol and treated with lysozyme. The problems of quantitative in situ analysis of Gram-Positive Bacteria with a low DNA G+C content in biofilm flocs are discussed and recommendations made. Members of the Bacillus sub-branch were detected in different abundances in activated sludge samples from different wastewater plants.
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complete 23s ribosomal rna sequences of gram Positive Bacteria with a low dna g c content
Systematic and Applied Microbiology, 1992Co-Authors: Wolfgang Ludwig, Gudrun Kirchhof, Norbert Klugbauer, Michael Weizenegger, Doris Betzl, Mathias Ehrmann, Christian Hertel, Sabine Jilg, Ralf Tatzel, Horst ZitzelsbergerAbstract:Summary The complete 23S rRNA primary structures of 14 gram-Positive Bacteria with a low DNA G+C content were determined. The sequences were compared with 50 published as well as unpublished complete 23S rRNA sequences from Bacteria. Based on previously published models, higher order structure analyses were performed and a consensus higher order structure model of the 23S rRNA from gram-Positive Bacteria with a low DNA G+C content was established. A tree reflecting the phylogenetic relationships among gram-Positive Bacteria with a low DNA G+C content was reconstructed and compared with a phylogenetic tree based on a comparable data set of 16S rRNA sequences. The topologies of the trees are in good agreement.
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gram Positive Bacteria with a high dna g c content are characterized by a common insertion within their 23s rrna genes
Microbiology, 1992Co-Authors: Carsten Roller, Wolfgang Ludwig, Karlheinz SchleiferAbstract:An insertion of about 100 bases within the central part of the 23S rRNA genes was found to be a phylogenetic marker for the Bacterial line of descent of Gram-Positive Bacteria with a high DNA G+C content. The insertion was present in 23S rRNA genes of 64 strains representing the major phylogenetic groups of Gram-Positive Bacteria with a high DNA G+C content, whereas it was not found in 23S rRNA genes of 55 (eu)Bacteria representing Gram-Positive Bacteria with a low DNA G+C content and all other known (eu)Bacterial phyla. The presence of the insertion could be easily demonstrated by comparative gel electrophoretic analysis of in vitro-amplified 23S rDNA fragments, which contained the insertion. The nucleotide sequences of the amplified fragments were determined and sequence similarities of at least 44% were found. The overall similarity values are lower than those of 16S and 23S rRNA sequences of the particular organism. Northern hybridization experiments indicated the presence of the insertion within the mature 23S rRNA of Corynebacterium glutamicum.
