Early evolutionary loss of the lipid A modifying enzyme PagP resulting in innate immune evasion in <i>Yersinia pestis</i>
Courtney E. Chandler, Erin Harberts, Mark Pelletier, Iyarit Thaipisuttikul, Jace W. Jones, Adeline M. Hajjar, Jason W. Sahl, David R. Goodlett, Aaron C. Pride, David A. Rasko, M. Stephen Trent, Russell E. Bishop, Robert K. Ernst
Abstract
Significance Immune evasion is a hallmark of Yersinia pestis pathogenesis, including loss of pathogen-associated patterns recognized by Toll-like receptors. During its life cycle, Y. pestis alternates 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 acyltransferase pagP , resulting in synthesis of a stealthy, hypoacylated lipid A structure absent in other Yersiniaceae. This provides evidence of lipid A as a crucial determinant in Y. pestis infectivity, pathogenesis, and host innate immune evasion and represents one of the earliest identified adaptations of Y. pestis from Yersinia pseudotuberculosis .