Early evolutionary loss of the lipid A modifying enzyme PagP resulting in innate immune evasion inYersinia pestis Journal Articles uri icon

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  • SignificanceImmune evasion is a hallmark ofYersinia pestispathogenesis, including loss of pathogen-associated patterns recognized by Toll-like receptors. During its life cycle,Y. pestisalternates between mammalian hosts and arthropod transmission vectors and concurrently remodels its membrane, specifically modifying the structure of the lipid A portion of its lipopolysaccharide recognized by TLR4-MD2. Genomic analysis identified a single-nucleotide polymorphism that results in a premature stop in translation of the lipid A acyltransferasepagP, resulting in synthesis of a stealthy, hypoacylated lipid A structure absent in other Yersiniaceae. This provides evidence of lipid A as a crucial determinant inY. pestisinfectivity, pathogenesis, and host innate immune evasion and represents one of the earliest identified adaptations ofY. pestisfromYersinia pseudotuberculosis.


  • Chandler, Courtney E
  • Harberts, Erin M
  • Pelletier, Mark R
  • Thaipisuttikul, Iyarit
  • Jones, Jace W
  • Hajjar, Adeline M
  • Sahl, Jason W
  • Goodlett, David R
  • Pride, Aaron C
  • Rasko, David A
  • Trent, M Stephen
  • Bishop, Russell
  • Ernst, Robert K

publication date

  • September 15, 2020