"Metaphilic" Cell-Penetrating Polypeptide-Vancomycin Conjugate Efficiently Eradicates Intracellular Bacteria via a Dual Mechanism.

ABSTRACT: Infections by intracellular pathogens are difficult to treat because of the poor accessibility of antibiotics to the pathogens encased by host cell membranes. As such, a strategy that can improve the membrane permeability of antibiotics would significantly increase their efficiency against the intracellular pathogens. Here, we report the design of an adaptive, metaphilic cell-penetrating polypeptide (CPP)-antibiotic conjugate (VPP-G) that can effectively eradicate the intracellular bacteria both in vitro and in vivo. VPP-G was synthesized by attaching vancomycin to a highly membrane-penetrative guanidinium-functionalized metaphilic CPP. VPP-G effectively kills not only extracellular but also far more challenging intracellular pathogens, such as S. aureus, methicillin-r

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC7760462 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature