PDBsum entry 5d6c

Immune system

PDB id: 5d6c

Contents

Protein chains

219 a.a.

210 a.a.

Ligands

57S ×2

ACT ×2

GOL

Metals

_CA ×4

Waters ×702

PDB id:

5d6c

Name:

Immune system

Title:

Structure of 4497 fab bound to synthetic wall teichoic acid fragment

Structure:

4497 antibody igk (vl and cl). Chain: a, l. Engineered: yes. 4497 antibody igg1 (vh and ch1). Chain: b, h. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Resolution:

1.72Å R-factor: 0.205 R-free: 0.238

Authors:

P.J.Lupardus,R.Fong

Key ref:

S.M.Lehar et al. (2015). Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature, 527, 323-328. PubMed id: 26536114 DOI: 10.1038/nature16057

Date:

12-Aug-15 Release date: 11-Nov-15

Protein chains

No UniProt id for this chain

Struc: 219 a.a.

Protein chains

No UniProt id for this chain

Struc: 210 a.a.

DOI no: 10.1038/nature16057

Nature 527:323-328 (2015)

PubMed id: 26536114

Novel antibody-antibiotic conjugate eliminates intracellular S. aureus.

S.M.Lehar, T.Pillow, M.Xu, L.Staben, K.K.Kajihara, R.Vandlen, L.DePalatis, H.Raab, W.L.Hazenbos, J.H.Morisaki, J.Kim, S.Park, M.Darwish, B.C.Lee, H.Hernandez, K.M.Loyet, P.Lupardus, R.Fong, D.Yan, C.Chalouni, E.Luis, Y.Khalfin, E.Plise, J.Cheong, J.P.Lyssikatos, M.Strandh, K.Koefoed, P.S.Andersen, J.A.Flygare, M.Wah Tan, E.J.Brown, S.Mariathasan.

ABSTRACT

Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody-antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody-antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections.