D-amino acid derivative-modified peptidoglycan and methods of use thereof
The present disclosure provides modified bacteria and modified peptidoglycan comprising modified D-amino acids; compositions comprising the modified bacteria or peptidoglycan; and methods of using the modified bacteria or peptidoglycan. The modified D-amino acids include a bioorthogonal functional group such as an azide, an alkyne or a norbornene group. Also provided are modified peptidoglycans conjugated to a molecule of interest via a linker.
1. A modified bacterial cell comprising a modified peptidoglycan, wherein the modified peptidoglycan comprises at least one modified D-amino acid, wherein the at least one modified D-amino acid is an azide-modified, an alkyne-modified, or a norbornene-modified D-amino acid.
2. The modified bacterial cell of claim 1 , wherein the bacterial cell is present intracellularly in a eukaryotic host cell.
3. The modified bacterial cell of claim 2 , wherein the eukaryotic host cell is a macrophage.
4. The modified bacterial cell of claim 1 , wherein the modified D-amino acid is an azide-modified D-amino acid.
5. The modified bacterial cell of claim 1 , wherein the modified D-amino acid is an alkyne-modified D-amino acid.
6. The modified bacterial cell of claim 4 , wherein the modified D-amino acid is a norbornene-modified D-amino acid.
7. A modified bacterial cell comprising a modified peptidoglycan, wherein the modified peptidoglycan comprises at least one modified D-amino acid conjugated to a reagent via a heterocycle, wherein the at least one modified D-amino acid is an azide-modified, an alkyne-modified, or a norbornene-modified D-amino acid, and the reagent is an azide-containing reagent, an alkynyl reagent or a norbornene-reactive reagent.
8. The modified bacterial cell of claim 7 , wherein the bacterial cell is present intracellularly in a eukaryotic host cell.
9. The modified bacterial cell of claim 7 , wherein the eukaryotic host cell is a macrophage.
10. The modified bacterial cell of claim 7 , wherein the reagent comprises a detectable label.
11. The modified bacterial cell of claim 10 , wherein the detectable label is a fluorescent label.
12. The modified bacterial cell of claim 10 , wherein the detectable label is a radioactive isotope.
13. The modified bacterial cell of claim 10 , wherein the detectable label is biotin.
14. The modified bacterial cell of claim 10 , wherein the detectable label is a peptide that can be detected by antibody binding.
15. The modified bacterial cell of claim 7 , wherein the reagent comprises a therapeutic agent.
16. The modified bacterial cell of claim 7 , wherein the reagent comprises an immunomodulatory molecule.
17. The modified bacterial cell of claim 7 , wherein the modified D-amino acid is an azide-modified D-amino acid, and the reagent is an alkynyl or phosphine reagent.
18. The modified bacterial cell of claim 7 , wherein the modified D-amino acid is an alkyne-modified D-amino acid, and the reagent is an azide or alkynyl reagent.
19. The modified bacterial cell of claim 7 , wherein the modified D-amino acid is a norbornene-modified D-amino acid, and the reagent is a norbornene-reactive agent.