Early evolutionary loss of the lipid A modifying enzyme PagP resulting in innate immune evasion in<i>Yersinia pestis</i>

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.

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