Total Synthesis Of Teixobactin

To cope with the global bacterial multidrug resistance, scientific communities have devoted significant efforts to develop novel antibiotics, particularly those with new modes of actions. Teixobactin, recently isolated from uncultured bacteria, is considered as a promising first-in-class drug candidate for clinical development. Herein, we report its total synthesis by a highly convergent Ser ligation approach and this strategy allows us to prepare several analogues of the natural product

Polyethylenimine-Modified Graphene Oxide as a Novel Antibacterial Agent and Its Synergistic Effect with Daptomycin for Methicillin-Resistant <i>Staphylococcus aureus</i>

An aqueous dispersion of polyethylenimine-modified graphene oxide (PEI-GO) was prepared via a one-step synthesis through an epoxy ring-opening reaction. PEI-GO exhibited bacterial growth inhibition activity on methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) with a minimum inhibitory concentration as low as 8 μg mL^–1. Time–kill curve assay and SYTOX Green assay showed the antibacterial activity and bacteria cell membrane permeability of PEI-GO, respectively. Most importantly, when PEI-GO was employed at 1–2 μg mL^–1, a synergistic effect with daptomycin to resensitize daptomycin-resistant MRSA was revealed. A synergistic effect between PEI-GO and daptomycin provides a possible way to increase bacterial killing and reduce the development of daptomycin resistance. The antibacterial activity of PEI-GO is attributed to the damaged cell membrane caused by the sharp edge and chain structure of the PEI-GO nanosheets as well as the high density of amine groups present in the PEI chains. Our results indicate that PEI-GO dispersion has a great potential for clinical pathogenic bacteria treatment