Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 Mar 2024
18 Mar 2024
Historique:
received:
03
10
2023
accepted:
01
03
2024
medline:
19
3
2024
pubmed:
19
3
2024
entrez:
19
3
2024
Statut:
epublish
Résumé
Type IV pili (T4P) are prevalent, polymeric surface structures in pathogenic bacteria, making them ideal targets for effective vaccines. However, bacteria have evolved efficient strategies to evade type IV pili-directed antibody responses. Neisseria meningitidis are prototypical type IV pili-expressing Gram-negative bacteria responsible for life threatening sepsis and meningitis. This species has evolved several genetic strategies to modify the surface of its type IV pili, changing pilin subunit amino acid sequence, nature of glycosylation and phosphoforms, but how these modifications affect antibody binding at the structural level is still unknown. Here, to explore this question, we determine cryo-electron microscopy (cryo-EM) structures of pili of different sequence types with sufficiently high resolution to visualize posttranslational modifications. We then generate nanobodies directed against type IV pili which alter pilus function in vitro and in vivo. Cyro-EM in combination with molecular dynamics simulation of the nanobody-pilus complexes reveals how the different types of pili surface modifications alter nanobody binding. Our findings shed light on the impressive complementarity between the different strategies used by bacteria to avoid antibody binding. Importantly, we also show that structural information can be used to make informed modifications in nanobodies as countermeasures to these immune evasion mechanisms.
Identifiants
pubmed: 38499587
doi: 10.1038/s41467-024-46677-y
pii: 10.1038/s41467-024-46677-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2414Informations de copyright
© 2024. The Author(s).
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