Therapeutic CMP-Nonulosonates against Multidrug-Resistant Neisseria gonorrhoeae.

ABSTRACT: Neisseria gonorrhoeae deploys a unique immune evasion strategy wherein the lacto-N-neotetraose termini of lipooligosaccharide (LOS) are "capped" by a surface LOS sialyltransferase (Lst), using extracellular host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation enhances complement resistance by recruiting factor H (FH; alternative complement pathway inhibitor) and also by limiting classical pathway activation. Sialylated LOS also engages inhibitory Siglecs on host leukocytes, dampening innate immunity. Previously, we showed that analogues of CMP-sialic acids (CMP-nonulosonates [CMP-NulOs]), such as CMP-Leg5,7Ac₂ and CMP-Neu5Ac9N₃, are also substrates for Lst. Incorporation of Leg5,7Ac₂ and Neu5Ac9N₃ into LOS results in

SUBMITTER: Gulati S 

PROVIDER: S-EPMC7321800 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature