Synthetic Cell-Penetrating Oligomers Deliver Antibiotics to Eradicate Intracellular Pathogens

Abstract

Bacteria have evolved a myriad of strategies for evading a host’s immune system defenses. One strategy involves bacteria invading and hiding inside of macrophage cells, shielding themselves from the harmful effects of an immune response. Since many antibiotics and other antimicrobial treatments cannot efficiently penetrate mammalian cell’s cytoplasmic membranes, we are limited in the treatment strategies we can recommend for intracellular bacterial infections. Thus, we need to develop an approach to eradicate evasive intracellular bacteria, or we risk patients suffering from recurring infections or worse, death. In this project, we aimed to enhance vancomycin’s cell-penetrating ability to effectively reduce the bacteria burden of macrophage cells infected with Methicillin-resistance Staphylococcus aureus (MRSA). To do this, we assembled a compound consisting of a synthetic cell-penetrating oligomer (delivery vehicle), vancomycin (antimicrobial agent), and a reducible disulfide linker (release mechanism). We successfully synthesized and characterized the antimicrobial compound and began extracellular and intracellular antimicrobial experiments to investigate the research hypothesis.