AI Article Synopsis
- Novel therapies are urgently needed to combat the growing issue of multidrug-resistant gonorrhea, particularly involving the immune evasion tactics used by the bacteria.
- Gonococci use a unique strategy to evade the immune response by capping their lipooligosaccharides (LOS) with sialic acid, which helps them resist complement and cationic peptides.
- Research shows that CMP-sialic acid analogs (CMP-NulOs) can make gonococci vulnerable again, and their effectiveness relies on the presence of certain immune components, particularly cathelicidins.
Article Abstract
Novel therapies to counteract multidrug-resistant gonorrhea are urgently needed. A unique gonococcal immune evasion strategy involves capping of lipooligosaccharide (LOS) with sialic acid by gonococcal sialyltransferase (Lst), utilizing host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation renders gonococci resistant to complement and cationic peptides, and down-regulates the inflammatory response by engaging siglecs. CMP-sialic acid analogs (CMP-nonulosonates [CMP-NulOs]) such as CMP-Leg5,7Ac2 and CMP-Kdn are also utilized by Lst. Incorporation of these NulO analogs into LOS maintains gonococci susceptible to complement. Intravaginal administration of CMP-Kdn or CMP-Leg5,7Ac2 attenuates gonococcal colonization of mouse vaginas. Here, we identify a key mechanism of action for the efficacy of CMP-NulOs. Surprisingly, CMP-NulOs remained effective in complement C1q-/- and C3-/- mice. LOS Neu5Ac, but not Leg5,7Ac2 or Kdn, conferred resistance to the cathelicidins LL-37 (human) and mouse cathelicidin-related antimicrobial peptide in vitro. CMP-NulOs were ineffective in Camp-/- mice, revealing that cathelicidins largely mediate the efficacy of therapeutic CMP-NulOs.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552427 | PMC |
| http://dx.doi.org/10.1093/infdis/jiaa438 | DOI Listing |
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