@article{3951, abstract = {The morphological term 'amoeboid' migration subsumes a number of rather distinct biophysical modes of cellular locomotion that range from blebbing motility to entirely actin-polymerization-based gliding. Here, we discuss the diverse principles of force generation and force transduction that lead to the distinct amoeboid phenotypes. We argue that shifting the balance between actin protrusion, actomyosin contraction, and adhesion to the extracellular substrate can explain the different modes of amoeboid movement and that blebbing and gliding are barely extreme variants of one common migration strategy. Depending on the cell type, physiological conditions or experimental manipulation, amoeboid cells can adopt the distinct mechanical modes of amoeboid migration.}, author = {Lämmermann, Tim and Michael Sixt}, journal = {Current Opinion in Cell Biology}, number = {5}, pages = {636 -- 644}, publisher = {Elsevier}, title = {{Mechanical modes of 'amoeboid' cell migration}}, doi = {10.1016/j.ceb.2009.05.003}, volume = {21}, year = {2009}, } @article{3952, abstract = {The mammalian actin-binding protein 1 (mAbp1, Hip-55, SH3P7) is phosphorylated by the nonreceptor tyrosine kinase Syk that has a fundamental effect for several beta(2) integrin (CD11/CD18)-mediated neutrophil functions. Live cell imaging showed a dynamic enrichment of enhanced green fluorescence protein-tagged mAbp1 at the phagocytic cup of neutrophil-like differentiated HL-60 cells during beta(2) integrin-mediated phagocytosis of serum-opsonized Escherichia coli. The genetic absence of Syk or its pharmacologic inhibition using piceatannol abrogated the proper localization of mAbp1 at the phagocytic cup. The genetic absence or down-regulation of mAbp1 using the RNA interference technique significantly compromised beta(2) integrin-mediated phagocytosis of serum-opsonized E coli or Salmonella typhimurium in vitro as well as clearance of S typhimurium infection in vivo. Moreover, the genetic absence of mAbp1 almost completely abrogated firm neutrophil adhesion under physiologic shear stress conditions in vitro as well as leukocyte adhesion and extravasation in inflamed cremaster muscle venules of mice treated with tumor-necrosis factor alpha. Functional analysis showed that the down-regulation of mAbp1 diminished the number of beta(2) integrin clusters in the high-affinity conformation under flow conditions. These unanticipated results define mAbp1 as a novel molecular player in integrin biology that is critical for phagocytosis and firm neutrophil adhesion under flow conditions.}, author = {Schymeinsky, Jürgen and Gerstl, Ronald and Mannigel, Ingrid and Niedung, Katy and Frommhold, David and Panthel, Klaus and Heesemann, Jürgen and Michael Sixt and Quast, Thomas and Kolanus, Waldemar and Mocsai, Attila and Wienands, Jürgen and Sperandio, Markus and Walzog, Barbara}, journal = {Blood}, number = {19}, pages = {4209 -- 4220}, publisher = {American Society of Hematology}, title = {{A fundamental role of mAbp1 in neutrophils: impact on β(2) integrin-mediated phagocytosis and adhesion in vivo}}, doi = {10.1182/blood-2009-02-206169}, volume = {114}, year = {2009}, } @article{3953, abstract = {CD4(+)CD25(+) regulatory T cell (Treg) entry into secondary lymphoid organs and local expansion is critical for their immunosuppressive function. Long-term application of the sphingosine-1 phosphate receptor agonist FTY720 exerts pleiotropic anti-inflammatory effects, whereas short-term FTY720 boosts antiviral immunity. In this study, we provide evidence that FTY720 potently inhibits Treg proliferation in vitro and in vivo without affecting their viability, phenotype, or in vitro immunosuppression. In contrast, adoptively transferred Treg exposed ex vivo to FTY720 lost their protective effects in murine models of acute glomerulonephritis and acute graft-vs-host disease. On a cellular level, FTY720 inhibits IL-2-induced STAT-5 phosphorylation, paralleled by a loss of FoxP3 expression during Treg expansion in vitro. Notably, loss of in vivo immunosuppression is not due to impaired migration to or localization within secondary lymphoid organs. We could even show a selective trapping of adoptively transferred Treg in inflammatory lymph nodes by FTY720. Finally, Treg isolated from animals systemically exposed to FTY720 also exhibit a significantly impaired proliferative response upon restimulation when compared with Treg isolated from solvent-treated animals. In summary, our data suggest that sphingosine-1 phosphate receptor-mediated signals induced by FTY720 abrogate their in vivo immunosuppressive potential by blocking IL-2 induced expansion, which is indispensable for their in vivo immunosuppressive activity.}, author = {Wolf, Anna Maria and Eller, Kathrin and Zeiser, Robert and Dürr, Christoph and Gerlach, Ulrike V and Michael Sixt and Markut, Lydia and Gastl, Guenther and Rosenkranz, Alexander R and Wolf, Dominik}, journal = {Journal of Immunology}, number = {6}, pages = {3751 -- 3760}, publisher = {American Association of Immunologists}, title = {{The sphingosine 1-phosphate receptor agonist FTY720 potently inhibits regulatory T cell proliferation in vitro and in vivo}}, doi = {10.4049/jimmunol.0901011}, volume = {183}, year = {2009}, } @article{3954, abstract = {The leading front of a cell can either protrude as an actin-free membrane bleb that is inflated by actomyosin-driven contractile forces, or as an actin-rich pseudopodium, a site where polymerizing actin filaments push out the membrane. Pushing filaments can only cause the membrane to protrude if the expanding actin network experiences a retrograde counter-force, which is usually provided by transmembrane receptors of the integrin family. Here we show that chemotactic dendritic cells mechanically adapt to the adhesive properties of their substrate by switching between integrin-mediated and integrin-independent locomotion. We found that on engaging the integrin-actin clutch, actin polymerization was entirely turned into protrusion, whereas on disengagement actin underwent slippage and retrograde flow. Remarkably, accelerated retrograde flow was balanced by an increased actin polymerization rate; therefore, cell shape and protrusion velocity remained constant on alternating substrates. Due to this adaptive response in polymerization dynamics, tracks of adhesive substrate did not dictate the path of the cells. Instead, directional guidance was exclusively provided by a soluble gradient of chemoattractant, which endowed these 'amoeboid' cells with extraordinary flexibility, enabling them to traverse almost every type of tissue.}, author = {Renkawitz, Jörg and Schumann, Kathrin and Weber, Michele and Lämmermann, Tim and Pflicke, Holger and Piel, Matthieu and Polleux, Julien and Spatz, Joachim and Sixt, Michael K}, journal = {Nature Cell Biology}, number = {12}, pages = {1438 -- 1443}, publisher = {Nature Publishing Group}, title = {{Adaptive force transmission in amoeboid cell migration}}, doi = {10.1038/ncb1992}, volume = {11}, year = {2009}, } @article{3955, abstract = {Although both processes occur at similar rates, leukocyte extravasation from the blood circulation is well investigated, whereas intravasation into lymphatic vessels has hardly been studied. In contrast to a common assumption-that intra- and extravasation follow similar molecular principles-we previously showed that lymphatic entry of dendritic cells (DCs) does not require integrin-mediated adhesive interactions. In this study, we demonstrate that DC-entry is also independent of pericellular proteolysis, raising the question of whether lymphatic vessels offer preexisting entry routes. We find that the perilymphatic basement membrane of initial lymphatic vessels is discontinuous and therefore leaves gaps for entering cells. Using a newly developed in situ live cell imaging approach that allows us to dynamically visualize the cells and their extracellular environment, we demonstrate that DCs enter through these discontinuities, which are transiently mechanically dilated by the passaging cells. We further show that penetration of the underlying lymphatic endothelial layer occurs through flap valves lacking continuous intercellular junctions. Together, we demonstrate free cellular communication between interstitium and lymphatic lumen.}, author = {Pflicke, Holger and Michael Sixt}, journal = {The Journal of Experimental Medicine}, number = {13}, pages = {2925 -- 2935}, publisher = {Rockefeller University Press}, title = {{Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels}}, doi = {10.1084/jem.20091739}, volume = {206}, year = {2009}, } @article{3966, abstract = {Persistent homology has proven to be a useful tool in a variety of contexts, including the recognition and measurement of shape characteristics of surfaces in ℝ3. Persistence pairs homology classes that are born and die in a filtration of a topological space, but does not pair its actual homology classes. For the sublevelset filtration of a surface in ℝ3, persistence has been extended to a pairing of essential classes using Reeb graphs. In this paper, we give an algebraic formulation that extends persistence to essential homology for any filtered space, present an algorithm to calculate it, and describe how it aids our ability to recognize shape features for codimension 1 submanifolds of Euclidean space. The extension derives from Poincaré duality but generalizes to nonmanifold spaces. We prove stability for general triangulated spaces and duality as well as symmetry for triangulated manifolds. }, author = {Cohen-Steiner, David and Herbert Edelsbrunner and Harer, John}, journal = {Foundations of Computational Mathematics}, number = {1}, pages = {79 -- 103}, publisher = {Springer}, title = {{Extending persistence using Poincare and Lefschetz duality}}, doi = {10.1007/s10208-008-9027-z}, volume = {9}, year = {2009}, } @inproceedings{3967, abstract = {Motivated by the measurement of local homology and of functions on noisy domains, we extend the notion of persistent homology to sequences of kernels, images, and cokernels of maps induced by inclusions in a filtration of pairs of spaces. Specifically, we note that persistence in this context is well defined, we prove that the persistence diagrams are stable, and we explain how to compute them.}, author = {Cohen-Steiner, David and Herbert Edelsbrunner and Harer, John and Morozov, Dmitriy}, pages = {1011 -- 1020}, publisher = {SIAM}, title = {{Persistent homology for kernels, images, and cokernels}}, year = {2009}, } @inproceedings{3968, abstract = {We describe an algorithm for segmenting three-dimensional medical imaging data modeled as a continuous function on a 3-manifold. It is related to watershed algorithms developed in image processing but is closer to its mathematical roots, which are Morse theory and homological algebra. It allows for the implicit treatment of an underlying mesh, thus combining the structural integrity of its mathematical foundations with the computational efficiency of image processing.}, author = {Edelsbrunner, Herbert and Harer, John}, location = {Zermatt, Switzerland}, pages = {36 -- 50}, publisher = {Springer}, title = {{The persistent Morse complex segmentation of a 3-manifold}}, doi = {10.1007/978-3-642-10470-1_4}, volume = {5903}, year = {2009}, } @article{4136, abstract = {Populations living in a spatially and temporally changing environment can adapt to the changing optimum and/or migrate toward favorable habitats. Here we extend previous analyses with a static optimum to allow the environment to vary in time as well as in space. The model follows both population dynamics and the trait mean under stabilizing selection, and the outcomes can be understood by comparing the loads due to genetic variance, dispersal, and temporal change. With fixed genetic variance, we obtain two regimes: (1) adaptation that is uniform along the environmental gradient and that responds to the moving optimum as expected for panmictic populations and when the spatial gradient is sufficiently steep, and (2) a population with limited range that adapts more slowly than the environmental optimum changes in both time and space; the population therefore becomes locally extinct and migrates toward suitable habitat. We also use a population‐genetic model with many loci to allow genetic variance to evolve, and we show that the only solution now has uniform adaptation.}, author = {Polechova, Jitka and Barton, Nicholas H and Marion, Glenn}, journal = {American Naturalist}, number = {5}, pages = {E186 -- E204}, publisher = {University of Chicago Press}, title = {{Species' range: Adaptation in space and time}}, doi = {10.1086/605958}, volume = {174}, year = {2009}, } @article{4143, abstract = {The migration of single cells and epithelial sheets is of great importance for gastrulation and organ formation in developing embryos and, if misregulated, can have dire consequences e.g. during cancer metastasis. A keystone of cell migration is the regulation of adhesive contacts, which are dynamically assembled and disassembled via endocytosis. Here, we discuss some of the basic concepts about the function of endocytic trafficking during cell migration: transport of integrins from the cell rear to the leading edge in fibroblasts; confinement of signalling to the front of single cells by endocytic transport of growth factors; regulation of movement coherence in multicellular sheets by cadherin turnover; and shaping of extracellular chemokine gradients. Taken together, endocytosis enables migrating cells and tissues to dynamically modulate their adhesion and signalling, allowing them to efficiently migrate through their extracellular environment.}, author = {Ulrich, Florian and Heisenberg, Carl-Philipp J}, journal = {Traffic}, number = {7}, pages = {811 -- 818}, publisher = {Wiley-Blackwell}, title = {{Trafficking and cell migration}}, doi = {10.1111/j.1600-0854.2009.00929.x}, volume = {10}, year = {2009}, } @article{4149, abstract = {An important step in the formation of all epithelial organs is the coordinated polarisation of their constituent cells. One of the factors thought to be crucial for this process is the extracellular matrix (ECM), which provides positional information for cells and directs polarity specification and epithelial cyst formation in 3D culture. However, in vivo evidence for the role of the ECM in epithelial tissue polarisation is scarce. To gain insight in the factors involved in establishing cell polarity during organogenesis, we are studying a group of epithelial cells called the Dorsal Forerunner Cells (DFCs) in zebrafish embryos. These cells migrate as a cluster towards the vegetal pole of the developing embryo, where they involute. During this process they polarise, and make foci that open up to form a ciliated lumen called Kupffer’s vesicle. We find that interfering with the deposition of components of the extracellular matrix, or with the intracellular anchors of the cells to the matrix, impairs the polarisation of the DFC’s and leads to subsequent defects in lumen formation. In addition, we have developed a method to culture the DFCs ex vivo, allowing us to precisely manipulate the extracellular environment. The possibility of combining the genetic study of Kupffer’s vesicle formation in the live embryo with cell biological techniques in organ culture make this system uniquely relevant for studying the role of the ECM in polarisation during organogenesis. }, author = {Soete, Gwen and Heisenberg, Carl-Philipp J}, journal = {Mechanisms of Development}, pages = {S168 -- S168}, publisher = {Elsevier}, title = {{The role of the extracellular matrix in Kupffer's vesicle formation in zebrafish}}, doi = {10.1016/j.mod.2009.06.391}, volume = {126}, year = {2009}, } @article{4158, abstract = {Together with cell growth, division and death, changes in cell shape are of central importance for tissue morphogenesis during development. Cell shape is the product of a cell's material and active properties balanced by external forces. Control of cell shape, therefore, relies on both tight regulation of intracellular mechanics and the cell's physical interaction with its environment. In this review, we first discuss the biological and physical mechanisms of cell shape control. We next examine a number of develop mental processes in which cell shape change - either individually or in a coordinated manner - drives embryonic morphogenesis and discuss how cell shape is controlled in these processes. Finally, we emphasize that cell shape control during tissue morphogenesis can only be fully understood by using a combination of cellular, molecular, developmental and biophysical approaches.}, author = {Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Current Biology}, number = {17}, pages = {R790 -- R799}, publisher = {Cell Press}, title = {{Biology and physics of cell shape changes in development}}, doi = {10.1016/j.cub.2009.07.029}, volume = {19}, year = {2009}, } @article{4159, abstract = {Apical cell contraction triggers tissue folding and invagination in epithelia. During Drosophila gastrulation, ventral furrow formation was thought to be driven by smooth, purse-string-like constriction of an actomyosin belt underlying adherens junctions. Now Martin et al. report in Nature that ventral furrow formation is triggered by asynchronous pulsed contractions of the apical acto-myosin cortex in individual cells.}, author = {Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {1}, pages = {4 -- 6}, publisher = {Cell Press}, title = {{Chaos begets order: Asynchronous cell contractions drive epithelial morphogenesis}}, doi = {10.1016/j.devcel.2008.12.011}, volume = {16}, year = {2009}, } @article{4160, abstract = {While the function of patterning in organogenesis is being extensively studied, considerably less is known of reverse effects that organ formation imposes on patterning. In zebrafish, the Kupffer’s vesicle (KV) and parapineal (PP) are embryonic struc- tures that share mechanisms of organogenesis and whose func- tion is essential for normal patterning along the left–right axis. Early morphogenesis of KV and PP organs involve the compaction of progenitor cells into a tight cluster within which three-dimen- sional cellular rosettes are formed. Organisation into rosettes pre- cedes the detachment of progenitor cells from neighbouring tissue and thus represents a key step towards organ formation. Such morphogenetic event is essential for organ function and its disruption has profound effects on left–right patterning.}, author = {Oteíza, Pablo and Lemus, Carmen and Köppen, Mathias and Palma, Karina and Krieg, Michael and Melo, Cristina and Farias, Cecilia and Pulgar, Eduardo and Preibisch, Steffen and Hartel, Steffen and Heisenberg, Carl-Philipp J and Concha, Miguel}, journal = {Mechanisms of Development}, number = {Supplement 1}, pages = {S11 -- S11}, publisher = {Elsevier}, title = {{Linking organ formation to left-right patterning in the embryonic zebrafish}}, doi = {10.1016/j.mod.2009.06.970}, volume = {126}, year = {2009}, } @article{4162, abstract = {Organ formation requires the precise assembly of progenitor cells into a functional unit. Mechanical forces are likely to play a critical role in this process, but it is unclear how these are molecularly controlled during development. Here, we show that Wnt11/ Pk1a-mediated planar cell polarity (PCP) signalling coordinates formation of the zebrafish laterality organ (Kupffer’s vesicle, KV) by regulating adhesion forces between organ progenitor cells (the dorsal forerunner cells, DFCs).}, author = {Oteíza, Pablo and Köppen, Mathias and Krieg, Michael and Preibisch, Steffen and Haertel, Steffen and Müller, Daniel and Heisenberg, Carl-Philipp J and Concha, Miguel}, journal = {Mechanisms of Development}, number = {Supplement 1}, pages = {S80 -- S80}, publisher = {Elsevier}, title = {{Wnt11/Pk1a-mediated planar cell polarity signalling orchestrates epithelial organ morphogenesis by regulating N-cadherin dependent cell adhesion forces}}, doi = {10.1016/j.mod.2009.06.098}, volume = {126}, year = {2009}, } @article{4165, abstract = {The tissues of a developing embryo are simultaneously patterned, moved and differentiated according to an exchange of information between their constituent cells. We argue that these complex self-organizing phenomena can only be fully understood with quantitative mathematical frameworks that allow specific hypotheses to be formulated and tested. The quantitative and dynamic imaging of growing embryos at the molecular, cellular and tissue level is the key experimental advance required to achieve this interaction between theory and experiment. Here we describe how mathematical modelling has become an invaluable method to integrate quantitative biological information across temporal and spatial scales, serving to connect the activity of regulatory molecules with the morphological development of organisms.}, author = {Oates, Andrew and Gorfinkiel, Nicole and Gonzalez Gaitan, Marcos and Heisenberg, Carl-Philipp J}, journal = {Nature Reviews Genetics}, number = {8}, pages = {517 -- 530}, publisher = {Nature Publishing Group}, title = {{Quantitative approaches in developmental biology}}, doi = {10.1038/nrg2548}, volume = {10}, year = {2009}, } @article{4192, abstract = {During vertebrate gastrulation, the body axis is established by a variety of co-ordinated and directed movements of cells. One of these movements is convergence and extension (CE), which is regulated by a non-canonical Wnt/planar cell polarity (PCP) pathway. From our forward genetic screen, we have identified 3-hydroxy-3-methyglutaryl-coenzyme A reductase 1b (hmgcr1b) gene as a dominant enhancer of the silberblick (slb)/wnt11 CE phenotype. hmgcr1b mutant embryos exhibit only very mild CE phenotype during gastrulation while showing a thicker yolk extension at pharyngula stages. Notably, abrogation of hmgcr1b also enhances the CE defects of other core PCP mutants/morphants. The prenylation pathway is one of branches downstream of HMGCR, and has been implicated for lipid modification at the C-terminus of proteins. To test the possibility that the prenylation pathway regulates activities of the PCP pathway, we abrogated farnesyl transferase (FT) or geranylgeranyl transferase (GGT) function using morpholinos on PCP mutant/morphant backgrounds. Consistent with the notion that FT preferentially performs lipid modification on to proteins with the CAAX motif including the core PCP protein Prickle (Pk), abrogation of FT, but not GGT, enhances the pk1a or pk1b morphant CE phenotype, suggesting the specif icity for targets of the prenylation enzymes. }, author = {Kai, Masatake and Buchan, Nina and Heisenberg, Carl-Philipp J and Tada, Masazumi}, journal = {Mechanisms of Development}, number = {Supplement 1}, pages = {S132 -- S132}, publisher = {Elsevier}, title = {{Regulation of planar cell polarity signalling by the prenylation pathway}}, doi = {10.1016/j.mod.2009.06.269}, volume = {126}, year = {2009}, } @article{4206, abstract = {Dorsal closure (DC), the closure of a hole in the dorsal epidermis of Drosophila embryos by the joining of opposing epithelial cell sheets, has been used as a model process to study the molecular and cellular mechanisms underlying epithelial spreading and wound healing. Recent studies have provided novel insights into how different tissues function cooperatively in this process. Specifically, they demonstrate a critical function of the epidermis surrounding the hole in modulating the behavior of the amnioserosa cells inside. These findings shed light not only on the mechanisms by which the behavior of different tissues is coordinated during DC, but also on the general mechanisms by which tissues interact to trigger global morphogenesis, an essential but yet poorly explored aspect of embryogenesis.}, author = {Heisenberg, Carl-Philipp J}, journal = {Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology}, number = {12}, pages = {1284 -- 1287}, publisher = {Wiley-Blackwell}, title = {{Dorsal closure in Drosophila: cells cannot get out of the tight spot}}, doi = {10.1002/bies.200900109}, volume = {31}, year = {2009}, } @article{4217, abstract = {Nuclear movements play an essential role in metazoan development. Although the intracellular transport mechanisms underlying nuclear movements have been studied in detail, relatively little is known about signals from surrounding cells and tissues controlling these movements. Here, we show that, in gastrulating zebrafish embryos, convergence movements of nuclei within the yolk syncytial layer (YSL) are guided by mesoderm and endoderm progenitors migrating along the surface of the yolk towards the dorsal side of the developing gastrula. Progenitor cells direct the convergence movements of internal yolk syncytial nuclei (iYSN) by modulating cortical flow within the YSL in which the iYSN are entrained. The effect of mesoderm and endoderm progenitors on the convergence movement of iYSN depends on the expression of E-cadherin, indicating that adhesive contact between the cells and the YSL is required for the mesendoderm-modulated YSL cortical flow mediating nuclear convergence. In summary, our data reveal a crucial function for cortical flow in the coordination of syncytial nuclear movements with surrounding cells and tissues during zebrafish gastrulation.}, author = {Carvalho, Lara and Stuehmer, Jan and Bois, Justin and Kalaidzidis, Yannis and Lecaudey, Virginie and Heisenberg, Carl-Philipp J}, journal = {Development}, number = {8}, pages = {1305 -- 1315}, publisher = {Company of Biologists}, title = {{Control of convergent yolk syncytial layer nuclear movement in zebrafish}}, doi = {10.1242/dev.026922}, volume = {136}, year = {2009}, } @article{4223, abstract = {Both Gram-positive and Gram-negative bacteria contain bactoprenol-dependent biosynthetic pathways expressing non-essential cell surface polysaccharides that function as virulence factors. Although these polymers are not required for bacterial viability in vitro, genes in many of the biosynthetic pathways are conditionally essential: they cannot be deleted except in strains incapable of initiating polymer synthesis. We report a cell-based, pathway-specific strategy to screen for small molecule inhibitors of conditionally essential enzymes. The screen identifies molecules that prevent the growth of a wildtype bacterial strain but do not affect the growth of a mutant strain incapable of initiating polymer synthesis. We have applied this approach to discover inhibitors of wall teichoic acid (WTA) biosynthesis in Staphylococcus aureus. WTAs are anionic cell surface polysaccharides required for host colonization that have been suggested as targets for new antimicrobials. We have identified a small molecule, 7-chloro-N,N-diethyl-3-(phenylsulfonyl)-[1,2,3]triazolo[1,5-a]quinolin-5-amine (1835F03), that inhibits the growth of a panel of S. aureus strains (MIC = 1−3 μg mL−1), including clinical methicillin-resistant S. aureus (MRSA) isolates. Using a combination of biochemistry and genetics, we have identified the molecular target as TarG, the transmembrane component of the ABC transporter that exports WTAs to the cell surface. We also show that preventing the completion of WTA biosynthesis once it has been initiated triggers growth arrest. The discovery of 1835F03 validates our chemical genetics strategy for identifying inhibitors of conditionally essential enzymes, and the strategy should be applicable to many other bactoprenol-dependent biosynthetic pathways in the pursuit of novel antibacterials and probes of bacterial stress responses.}, author = {Swoboda, Jonathan and Meredith, Timothy and Campbell, Jennifer and Brown, Stephanie and Suzuki, Takashi and Bollenbach, Mark Tobias and Malhowski, Amy and Kishony, Roy and Gilmore, Michael and Walker, Suzanne}, journal = {ACS Chemical Biology}, number = {10}, pages = {875 -- 883}, publisher = {American Chemical Society}, title = {{Discovery of a Small Molecule that Blocks Wall Teichoic Acid Biosynthesis in Staphylococcus aureus}}, doi = {10.1021/cb900151k}, volume = {4}, year = {2009}, }