Transition transferases prime bacterial capsule polymerization
Nature Chemical Biology, vol. 21, pp. 120–130
Abstract
Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane. Using Actinobacillus pleuropneumoniae as an example, we demonstrate that CpsA and CpsC generate a poly(glycerol-3-phosphate) linker to connect the glycolipid with capsules containing poly(galactosylglycerol-phosphate) backbones. We reconstruct the entire capsule biosynthesis pathway in A. pleuropneumoniae serotypes 3 and 7, solve the X-ray crystal structure of the capsule polymerase CpsD, identify its tetratricopeptide repeat domain as essential for elongating poly(glycerol-3-phosphate) and show that CpsA and CpsC stimulate CpsD to produce longer polymers. We identify the CpsA and CpsC product as a wall teichoic acid homolog, demonstrating similarity between the biosynthesis of Gram-positive wall teichoic acid and Gram-negative capsules.
Authors 20
-
Medizinische Hochschule Hannover · German Center for Infection Research
Affiliation as printed
German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
Consejo Superior de Investigaciones Científicas · BioCruces Health research Institute · Hospital de Cruces · Institut de Biologia Molecular de Barcelona · Parc Científic de Barcelona
Affiliation as printed
Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Barakaldo, Spain
Structural Glycobiology Laboratory, Department of Structural and Molecular Biology; Molecular Biology Institute of Barcelona, Spanish National Research Council, Barcelona Science Park, Tower R, Barcelona, Spain
-
Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
Sizhe Li Aachen
Affiliation as printed
Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
-
Affiliation as printed
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
-
Thijs Voskuilen Aachen
Affiliation as printed
Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
-
Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
BioCruces Health research Institute · CIC bioGUNE · Hospital de Cruces
Affiliation as printed
Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Barakaldo, Spain
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, Bizkaia Technology Park, Derio, Spain
-
Affiliation as printed
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, Bizkaia Technology Park, Derio, Spain
-
Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
-
University of Augsburg · Medizinische Hochschule Hannover
Affiliation as printed
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
Proteomics, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany
-
University of Alberta · National Taiwan University · Institute of Biological Chemistry, Academia Sinica · Academia Sinica
Affiliation as printed
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
-
Affiliation as printed
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
-
Jeroen D. C. Codée Aachen
Affiliation as printed
Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
-
University of Salzburg · Freie Universität Berlin
Affiliation as printed
Department of Biology, Chemistry and Pharmacy, Free University of Berlin, Berlin, Germany
Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria
-
Marcelo E. Guerin corresponding
Ikerbasque · Consejo Superior de Investigaciones Científicas · BioCruces Health research Institute · CIC bioGUNE · Hospital de Cruces · Institut de Biologia Molecular de Barcelona · Parc Científic de Barcelona
Affiliation as printed
Ikerbasque, Basque Foundation for Science, Bilbao, Spain. mrccri@ibmb.csic.es
Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Barakaldo, Spain. mrccri@ibmb.csic.es
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, Bizkaia Technology Park, Derio, Spain. mrccri@ibmb.csic.es
Structural Glycobiology Laboratory, Department of Structural and Molecular Biology; Molecular Biology Institute of Barcelona, Spanish National Research Council, Barcelona Science Park, Tower R, Barcelona, Spain. mrccri@ibmb.csic.es
-
Timm Fiebig corresponding
Medizinische Hochschule Hannover · German Center for Infection Research
Affiliation as printed
German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany. Fiebig.Timm@mh-hannover.de
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany. Fiebig.Timm@mh-hannover.de
Cited by 9 stored of 9
9 results
No patents citing this paper on Lens.org (checked 2026-10-11).