Vitamin B12 Carries Peptide Nucleic Acids to E. Coli Cells through the Outer-Membrane BtuB Receptor

Short oligonucleotides binding complementary mRNA essential for bacterial growth could be used as antibacterials provided that they are delivered to cells. One promising oligonucleotide is peptide nucleic acid (PNA), a synthetic DNA analog with neutral peptide-like backbone. Unfortunately, bacteria do not import short oligonucleotides, including PNA, from the environment and efficient non-invasive methods PNA delivery have been found. To deliver cells, we vitamin B12. Most need B12 sustain life. We shown covalently linked delivers E. coli Free enters via TonB-dependent transport system recognized by outer-membrane B12-specific BtuB receptor. engineered ΔbtuB mutant found of B12-PNA conjugate also requires BtuB. Thus, uses receptor through outer membrane. Overall, proven can hijacked Further, using Gaussian-force simulated annealing molecular dynamics umbrella sampling determined mechanism permeation protein. beta-barrel occluded its luminal domain, but partial unfolding this domain makes passage mechanically feasible. movement into energetically favorable since, while inside BtuB, extends. In addition, extracellular loops actively involved in an induced-fit mechanism.