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| Open AccessA comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus
Poly-β-(1–6)-N-acetylglucosamine (PNAG) is an important vaccine target, but the impact of the number and position of free amine vs N-acetylation on its antigenicity is not well understood. Here, the authors report a divergent strategy to synthesize a comprehensive library of PNAG pentasaccharides, enabling the identification of enhanced epitopes for vaccines against Staphylococcus aureus including drug resistant strains.
- Zibin Tan
- , Weizhun Yang
- & Xuefei Huang
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Article
| Open AccessStructural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans
Carbohydrate binding modules (CBMs) are non-catalytic domains found within multi-modular carbohydrate-active enzymes like glycoside hydrolases. Here, the authors show the crystal structures of two CBM family 92 members, which use three different surface binding sites to bind to β-glucans.
- Meng-Shu Hao
- , Scott Mazurkewich
- & Lauren S. McKee
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| Open AccessStructure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens
Here, the authors present the structure of cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens, revealing a distinct mechanism that uses a tyrosine-linked oligosaccharide intermediate in cycles of polymerization and processing of the glucan chain.
- Jaroslaw Sedzicki
- , Dongchun Ni
- & Christoph Dehio
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| Open AccessStructural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1
Heparan sulfate biosynthesis is a complex process involving multiple reactions that extend and modify the polysaccharide. Here, the authors resolve structures of NDST1, responsible for the critical N-sulfoglucosamine modification of heparan sulfate.
- Courtney J. Mycroft-West
- , Sahar Abdelkarim
- & Liang Wu
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Article
| Open AccessStructural adaptation of fungal cell wall in hypersaline environment
Solid-state NMR snapshots of Aspergillus sydowii and other halophilic fungal species reveal the structural rearrangement of polysaccharides and proteins, which create a thick, stiff and hydrophobic cell wall to withstand external stress and thrive in hypersaline environment
- Liyanage D. Fernando
- , Yordanis Pérez-Llano
- & Tuo Wang
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Article
| Open AccessSpatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis
Spatial metabolomics are used to describe the location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice.
- Lindsey R. Conroy
- , Harrison A. Clarke
- & Ramon C. Sun
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Article
| Open AccessIdentification of d-arabinan-degrading enzymes in mycobacteria
Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, the authors identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria.
- Omar Al-Jourani
- , Samuel T. Benedict
- & Patrick J. Moynihan
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Article
| Open AccessHedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient
The Hedgehog morphogen creates gradients during development, but diffusion alone cannot explain its spatiotemporal dynamics. Hedgehog transport requires binding heparan sulfate sugar chains, and the authors now show that Hedgehogs can spread by interacting with sequential heparan molecules.
- Fabian Gude
- , Jurij Froese
- & Kay Grobe
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Article
| Open AccessChemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors
Heparin is a family of complex carbohydrates binding to proteins to modulate cell activities. Here the authors report the synthesis, and conformations simulations of S-linked hemi-A heparosan [GlcA-S-GlcNAc]n, a thio-glycosidic uncleavable polysaccharide, and test it as human heparanase inhibitor.
- Peng He
- , Xing Zhang
- & Paul L. DeAngelis
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Article
| Open AccessMolecular basis for glycan recognition and reaction priming of eukaryotic oligosaccharyltransferase
Oligosaccharyltransferase (OST), the central enzyme in N-glycosylation, modifies acceptor proteins by attaching a complex glycan. Cryo-EM structures of OST in distinct states, reveal the molecular basis of substrate recognition and catalysis.
- Ana S. Ramírez
- , Mario de Capitani
- & Kaspar P. Locher
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Article
| Open AccessN6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA
Here the authors find that the mRNA of GYS2, the liver-specific glycogen synthase, is a substrate of METTL3 and IGF2BP2 and that m6A-mediated regulation of Gys2 mRNA is critical for the maintenance of liver glycogenesis in mammals during growth, such as mice and rats.
- Xiang Zhang
- , Huilong Yin
- & Rui Zhang
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Article
| Open AccessA pathway for chitin oxidation in marine bacteria
Lytic polysaccharide monooxygenases contribute to microbial degradation of chitin, but how the resulting oxidized chitooligosaccharides are utilized by microbes is unclear. Here, the authors describe a complete pathway for oxidative chitin utilization in marine bacteria.
- Wen-Xin Jiang
- , Ping-Yi Li
- & Yu-Zhong Zhang
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Article
| Open AccessSynthetic phosphoethanolamine-modified oligosaccharides reveal the importance of glycan length and substitution in biofilm-inspired assemblies
The phosphoethanolamine modified cellulose in E. colibiofilms has revealed that polysaccharide functionalization alters the biofilm properties. Here, the authors show a model system to explore the role of phosphoethanolamine and other unnatural modifications on the properties of the biofilm-inspired assemblies.
- Theodore Tyrikos-Ergas
- , Soeun Gim
- & Martina Delbianco
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| Open AccessElucidating Human Milk Oligosaccharide biosynthetic genes through network-based multi-omics integration
Human milk oligosaccharides are fundamental to infant health. Here the authors deploy a multi-omics systems biology approach to elucidate their biosynthetic network, including the associated enzymes and likely structures of ambiguous oligosaccharides.
- Benjamin P. Kellman
- , Anne Richelle
- & Nathan E. Lewis
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Article
| Open AccessPplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides
The cell wall of the bacterial pathogen Group A Streptococcus is decorated with a polysaccharide termed GAC, which is a target for vaccine development. Here, Rush et al. characterize the linkage between GAC and peptidoglycan, and identify a protein that deacetylates the linkage and thus protects the pathogen against host cationic antimicrobial proteins.
- Jeffrey S. Rush
- , Prakash Parajuli
- & Natalia Korotkova
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Article
| Open AccessCarbohydrate-aromatic interface and molecular architecture of lignocellulose
The plant biomass is a composite formed by a variety of polysaccharides and an aromatic polymer named lignin. Here, the authors use solid-state NMR spectroscopy to unveil the carbohydrate-aromatic interface that leads to the variable architecture of lignocellulose biomaterials.
- Alex Kirui
- , Wancheng Zhao
- & Tuo Wang
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Article
| Open AccessCoalescence and directed anisotropic growth of starch granule initials in subdomains of Arabidopsis thaliana chloroplasts
Starch is the major form of energy storage in plant cells and forms discrete, semi-crystalline granules within plastids. Here the authors use electron tomography and nanoSIMS to show that Arabidopsis starch granules initiate in stromal pockets between thylakoid membranes that coalesce before growing anisotropically.
- Léo Bürgy
- , Simona Eicke
- & Samuel C. Zeeman
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Article
| Open AccessA molecular vision of fungal cell wall organization by functional genomics and solid-state NMR
The fungal cell wall is a complex structure composed mainly of glucans, chitin and glycoproteins. Here, the authors use solid-state NMR spectroscopy to assess the cell wall architecture of Aspergillus fumigatus, comparing wild-type cells and mutants lacking major structural polysaccharides, with insights into the distinct functions of these components.
- Arnab Chakraborty
- , Liyanage D. Fernando
- & Tuo Wang
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| Open AccessDiscovery of fungal oligosaccharide-oxidising flavo-enzymes with previously unknown substrates, redox-activity profiles and interplay with LPMOs
Microbial oxidoreductases are key in biomass breakdown. Here, the authors expand the specificity and redox scope within fungal auxiliary activity 7 family (AA7) enzymes and show that AA7 oligosaccharide dehydrogenases can directly fuel cellulose degradation by lytic polysaccharide monooxygenases.
- Majid Haddad Momeni
- , Folmer Fredslund
- & Maher Abou Hachem
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Article
| Open AccessDiatom fucan polysaccharide precipitates carbon during algal blooms
The fate of ocean carbon is determined by the balance between primary productivity and heterotrophic breakdown of that photosynthate. Here the authors show that diatoms produce a polysaccharide that resists bacterial degradation, accumulates, aggregates and stores carbon during spring blooms.
- Silvia Vidal-Melgosa
- , Andreas Sichert
- & Jan-Hendrik Hehemann
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Article
| Open AccessStructure of a full-length bacterial polysaccharide co-polymerase
Lipopolysaccharides, important components of the bacterial cell envelope, are synthesized at the inner membrane by the Wzx/Wzy-dependent assembly pathway. A cryo-EM structure of an intact E. coli WzzB, the polysaccharide co-polymerase component of this pathway, reveals details of the transmembrane, cytoplasmic domains and a conserved a proline-rich segment proximal to the C-terminal transmembrane helix.
- Benjamin Wiseman
- , Ram Gopal Nitharwal
- & Martin Högbom
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Article
| Open AccessStructural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A
Neisseria meningitidis capsular polysaccharide (CPS) is a major virulence factor and vaccine formulations against Neisseria meningitidis serogroup A (NmA) contain O-acetylated CPS. Here, the authors provide mechanistic insights into CPS O-acetylation in NmA by determining the crystal structure of the O-acetyltransferase CsaC and NMR measurements further reveal that the CsaC-mediated reaction is regioselective for O3 and that the O4 modification results from spontaneous O-acetyl migration.
- Timm Fiebig
- , Johannes T. Cramer
- & Martina Mühlenhoff
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| Open AccessWood hemicelluloses exert distinct biomechanical contributions to cellulose fibrillar networks
Hemicelluloses are an essential constituent of plant cell walls, but the individual biomechanical roles remain elusive. Here the authors report on the interaction of wood hemicellulose with bacterial cellulose during deposition and explore the resultant fibrillar architecture and mechanical properties.
- Jennie Berglund
- , Deirdre Mikkelsen
- & Francisco Vilaplana
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| Open AccessA nonenzymatic method for cleaving polysaccharides to yield oligosaccharides for structural analysis
While mass spectrometry-based proteomics largely relies on digesting proteins into peptides, there is no equivalent strategy for polysaccharide analysis. Here, the authors develop a chemical approach to break down poly- into oligosaccharides and present a workflow to identify polysaccharides by oligosaccharide fingerprinting.
- Matthew J. Amicucci
- , Eshani Nandita
- & Carlito B. Lebrilla
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| Open AccessEliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
Bioproduction of hyaluronan needs increases in yield and greater diversity of the molecular weights. Here, the author increases hyaluronan production and diversifies the molecular weights through engineering the hyaluronan biosynthesis pathway and disruption of Corynebacterium glutamicum encapsulation caused by secreted hyaluronan.
- Yang Wang
- , Litao Hu
- & Zhen Kang
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Article
| Open AccessMetabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus
Glycosaminoglycans (GAGs) are an important nutrient source for the gut microbiome. Here, the authors characterize the genetic loci that underpins glycosaminoglycan utilization in Bacteroides thetaiotaomicron; providing insights into the metabolism of GAGs by a predominant member of the gut microbiota.
- Didier Ndeh
- , Arnaud Baslé
- & Alan Cartmell
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| Open AccessMolecular architecture of softwood revealed by solid-state NMR
Understanding the interactions between the constituents of the cell walls in wood is important for understanding the mechanical properties. Here, the authors report on a solid-state NMR study of never-dried softwood, noticing differences to previous reports and develop a model of softwood architecture.
- Oliver M. Terrett
- , Jan J. Lyczakowski
- & Paul Dupree
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| Open AccessBacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification
Glycan molecules can be modified directly on the cell surface via chemoenzymatic approaches. Here, the authors employ a set of four bacterial glycosyltransferases to develop a live cell-based killing assay to probe host cell glycan-mediated influenza A virus infection.
- Senlian Hong
- , Yujie Shi
- & Peng Wu
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Article
| Open AccessLignin-polysaccharide interactions in plant secondary cell walls revealed by solid-state NMR
The interactions of lignin with polysaccharides in plant secondary cell walls are not well understood. Here the authors employ solid-state NMR measurements to analyse intact stems of maize, Arabidopsis, switchgrass and rice and observe that lignin self-aggregates and forms highly hydrophobic microdomains that make extensive surface contacts to xylan.
- Xue Kang
- , Alex Kirui
- & Tuo Wang
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Article
| Open AccessHemocyanin facilitates lignocellulose digestion by wood-boring marine crustaceans
Marine woodborers can digest woody biomass without the help of gut microbiota but the mechanism has remained unclear. Here, the authors provide evidence that the woodborer’s respiratory protein hemocyanin plays a central role in wood digestion and may offer a route toward biorefining of woody plant biomass.
- Katrin Besser
- , Graham P. Malyon
- & Simon J. McQueen-Mason
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Article
| Open AccessEngineering enhanced cellobiohydrolase activity
Cellobiohydrolases (CBHs) are critical for natural and industrial biomass degradation but their structure–activity relationships are not fully understood. Here, the authors present the biochemical and structural characterization of two CBHs, identifying protein regions that confer enhanced CBH activity.
- Larry E. Taylor II
- , Brandon C. Knott
- & Gregg T. Beckham
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Article
| Open AccessMolecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont
Polysaccharides are the primary structural cell wall and energy storage molecules of seaweed. Here, the authors show how the geographically restricted dietary polysaccharide agarose is selectively utilized by the human intestinal bacterium Bacteroides uniformis, providing insight into how carbohydrate metabolism evolves within the human microbiome.
- Benjamin Pluvinage
- , Julie M. Grondin
- & D. Wade Abbott
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| Open AccessAn ancient family of lytic polysaccharide monooxygenases with roles in arthropod development and biomass digestion
LPMOs catalyze the oxidative breakdown of polysaccharides, thereby facilitating biomass degradation. By analyzing the digestive proteome of firebrats, the authors here identify a yet uncharacterized LPMO family and provide phylogenetic, structural and biochemical insights into its origin and functions.
- Federico Sabbadin
- , Glyn R. Hemsworth
- & Simon J. McQueen-Mason
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| Open AccessDeciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens
Melioidosis and glanders are multifaceted infections caused by gram-negative bacteria. Here, the authors synthesize a series of oligosaccharides that mimic the lipopolysaccharides present on the pathogens’ surface and use them to develop novel glycoconjugates for vaccine development.
- Marielle Tamigney Kenfack
- , Marcelina Mazur
- & Charles Gauthier
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| Open AccessMetabolic labelling of the carbohydrate core in bacterial peptidoglycan and its applications
N-acetyl-muramic acid (NAM) is a core component of the bacterial peptidoglycan (PG) cell wall, and is recognised by the innate immune system. Here the authors engineer Gram-negative and Gram-positive bacteria to incorporate a modified NAM into the backbone of PG, which can be labelled with click chemistry for imaging and tracking.
- Hai Liang
- , Kristen E. DeMeester
- & Catherine L. Grimes
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| Open Access[Au]/[Ag]-catalysed expedient synthesis of branched heneicosafuranosyl arabinogalactan motif of Mycobacterium tuberculosis cell wall
Arabinogalactan forms parts of the cellular envelope ofMycobacterium tuberculosis, however due to its size chemical synthesis is a massive task. Here the authors report the synthesis of branched heneicosafuranosyl arabinogalactan fragment by repeated use of a Au/Ag-catalysed glycosylation methodology.
- Shivaji A. Thadke
- , Bijoyananda Mishra
- & Srinivas Hotha
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Article
| Open AccessFolding of xylan onto cellulose fibrils in plant cell walls revealed by solid-state NMR
The polysaccharide xylan binds to cellulose microfibrils in the plant cell wall, but the nature of this interaction remains unclear. Here Simmonset al. show that while xylan forms a threefold helical screw in solution it forms a twofold screw to bind cellulose microfibrils in the plant cell wall.
- Thomas J. Simmons
- , Jenny C. Mortimer
- & Paul Dupree
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Article
| Open AccessAutomated assembly of oligosaccharides containing multiple cis-glycosidic linkages
Automated glycan assembly has proven a powerful method to rapidly synthesize large oligosaccharides, though stereoselective cis-glycosylation remains a challenge. Here, the authors demonstrate a system to selectively incorporate multiple cis-glycosidic linkages by use of remote participating groups.
- Heung Sik Hahm
- , Mattan Hurevich
- & Peter H Seeberger
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Article
| Open AccessThiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis
When grown in the lab, Mycobacterium tuberculosis can form pellicle biofilms. Here, Trivedi et al. show that thiol reductive stress (induced by dithiothreitol) triggers rapid formation of thicker biofilms containing cellulose as well as antibiotic-tolerant, metabolically active bacteria.
- Abhishek Trivedi
- , Parminder Singh Mavi
- & Ashwani Kumar
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Article
| Open AccessLight-driven oxidation of polysaccharides by photosynthetic pigments and a metalloenzyme
Lytic polysaccharide monooxygenases are proteins involved in the degradation of plant biomass and are promising biotechnological tools for biofuel production. Here, the authors show that their catalytic activity is significantly boosted when they are combined with photopigments and exposed to light.
- D. Cannella
- , K. B. Möllers
- & C. Felby
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Article
| Open AccessGut immunity in a protochordate involves a secreted immunoglobulin-type mediator binding host chitin and bacteria
Protochordates, including Ciona intestinalis, lack an adaptive immune system but possess innate immune receptors, including the secreted immunoglobulin V-region-containing VCBPs. Here the authors show that VCBP-C of Cionabinds gut bacteria and chitin-rich gut mucosa, influences biofilm formation and likely plays a role in gut homeostasis.
- Larry J. Dishaw
- , Brittany Leigh
- & Gary W. Litman
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Article
| Open AccessGlycan complexity dictates microbial resource allocation in the large intestine
The human gut microbiota helps us to degrade complex dietary carbohydrates such as xylan and, in turn, the carbohydrate breakdown products control the structure of the microbiota. Here the authors characterize the xylan-degrading apparatus of a key member of the gut microbiota, Bacteroides ovatus.
- Artur Rogowski
- , Jonathon A. Briggs
- & David N. Bolam
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Article
| Open AccessUnderstanding nanocellulose chirality and structure–properties relationship at the single fibril level
Cellulose is a material found in many different biological systems, but the fine structure at the single-molecule level is still being assessed. Here, the authors present high-resolution imaging of cellulose structures at the single particle level, finding evidence of chirality in bundles and fibrils.
- Ivan Usov
- , Gustav Nyström
- & Raffaele Mezzenga
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| Open AccessMolecular basis for bacterial peptidoglycan recognition by LysM domains
Proteins containing LysM domains recognize polysaccharides such as chitin and peptidoglycan, the main components of fungal and bacterial cell walls. Here the authors describe the molecular interactions between peptidoglycan and a LysM domain from the opportunistic bacterial pathogen Enterococcus faecalis.
- Stéphane Mesnage
- , Mariano Dellarole
- & Michael P. Williamson
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Article
| Open AccessCell wall elongation mode in Gram-negative bacteria is determined by peptidoglycan architecture
Bacterial cell wall peptidoglycan is essential for viability and shape determination. Using high-resolution microscopy, Foster and colleagues elucidate the peptidoglycan architecture and insertion pattern in Escherichia coliand other Gram-negative bacteria, and propose a new model for cell wall elongation.
- Robert D. Turner
- , Alexander F. Hurd
- & Simon J. Foster