Opis

• Tytuł:
  Preference of bacterial rhamnosyltransferases for 6‑deoxysugars reveals a strategy to deplete O‑antigens
• Twórca:
  Harnagel, Alexa P.;
  Sheshova, Mia;
  Zheng, Meng;
  Zheng, Maggie;
  Skorupinska-Tudek, Karolina;
  Swiezewska, Ewa;
  Lupoli, Tania J.
• Opis:
  Bacteria synthesize hundreds of bacteria-specific or “rare” sugars that are absent in mammalian cells and enriched in 6-deoxy monosaccharides such as L-rhamnose (L-Rha). Across bacteria, L-Rha is incorporated into glycans by rhamnosyltransferases (RTs) that couple nucleotide sugar substrates (donors) to target biomolecules (acceptors). Since L-Rha is required for the biosynthesis of bacterial glycans involved in survival or host infection, RTs represent potential antibiotic or antivirulence targets. However, purified RTs and their unique bacterial sugar substrates have been difficult to obtain. Here, we use synthetic nucleotide rare sugar and glycolipid analogs to examine substrate recognition by three RTs that produce cell envelope components in diverse species, including a known pathogen. We find that bacterial RTs prefer pyrimidine nucleotide-linked 6-deoxysugars, not those containing a C6-hydroxyl, as donors. While glycolipid acceptors must contain a lipid, isoprenoid chain length, and stereochemistry can vary. Based on these observations, we demonstrate that a 6-deoxysugar transition state analog inhibits an RT in vitro and reduces levels of RT-dependent O-antigen polysaccharides in Gram-negative cells. As O-antigens are virulence factors, bacteria-specific sugar transferase inhibition represents a novel strategy to prevent bacterial infections.
• Dostępność obiektu:
  Dostęp otwarty
• Data:
  2023
• Typ:
  Article;
  PeerReviewed
• Język:
  angielski
• Format:
  application/pdf
• Wydawca:
  ACS Publications
• Relacja: http://eprints.ibb.waw.pl/2307 ;https://pubs.acs.org/doi/10.1021/jacs.3c03005 ;doi: 10.1021/jacs.3c03005
• Temat i słowa kluczowe:
  QH301 Biology
• Identyfikator: http://eprints.ibb.waw.pl/2307/1/2023_JACS_Skorupinska.pdf ;
  Harnagel, Alexa P. and Sheshova, Mia and Zheng, Meng and Zheng, Maggie and Skorupinska-Tudek, Karolina and Swiezewska, Ewa and Lupoli, Tania J. (2023) Preference of bacterial rhamnosyltransferases for 6‑deoxysugars reveals a strategy to deplete O‑antigens. Journal of American Chemical Society, 145 . pp. 15639-15646.
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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