title: An iron-containing dodecameric heptosyltransferase family modifies bacterial autotransporters in pathogenesis.
abstract: Autotransporters deliver virulence factors to the bacterial surface by translocating an effector passenger domain through a membrane-anchored barrel structure. Although passenger domains are diverse, those found in enteric bacteria autotransporters, including AIDA-I in diffusely adhering Escherichia coli (DAEC) and TibA in enterotoxigenic E. coli, are commonly glycosylated. We show that AIDA-I is heptosylated within the bacterial cytoplasm by autotransporter adhesin heptosyltransferase (AAH) and its paralogue AAH2. AIDA-I heptosylation determines DAEC adhesion to host cells. AAH/AAH2 define a bacterial autotransporter heptosyltransferase (BAHT) family that contains ferric ion and adopts a dodecamer assembly. Structural analyses of the heptosylated TibA passenger domain reveal 35 heptose conjugates forming patterned and solenoid-like arrays on the surface of a β helix. Additionally, CARC, the AIDA-like autotransporter from Citrobacter rodentium, is essential for colonization in mice and requires heptosylation by its cognate BAHT. Our study establishes a bacterial glycosylation system that regulates virulence and is essential for pathogenesis.
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Lu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; College of Biological Sciences, China Agricultural University, Beijing 100094, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Analytical Chemistry & Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Gao
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Sharon
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Ben-Nissan
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, A-1190 Vienna, Austria.
authors.forename: Alla
authors.initials: A
authors.lastname: Zamyatina
authors.affiliation: Institute of Analytical Chemistry & Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China. Electronic address: shaofeng@nibs.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
mesh_terms: D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D044082:Citrobacter rodentium / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D004927:Escherichia coli Infections / Q000382:microbiology; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014774:Virulence
chemical_list: C075559:AIDA-I protein, E coli; D018830:Adhesins, Escherichia coli; D007501:Iron; D016695:Glycosyltransferases; C086735:heptosyltransferase