Antibacterial activities of functional groups on the benzene rings in nucleic acid nanocarriers

As bacterial membrane affects drug movements and causes drug resistance, membranolytic agents have been developed to target drug-resistant strains. Natural aromatic compounds are proven to inhibit bacterial growth through the hydrophobic interaction between their functional groups and bacterial membranes. This study proposes that natural aromatic compounds crosslinked with naturally-derived nucleic acids can serve as a membranolytic agent. The study also investigates if the functional groups on the aromatic benzene rings affect the antibacterial activity. Herein, 4-hydroxy-benzaldehyde (HB), ethylvanillin (EV), isovanillin (IV) and syringaldehyde (SY) were crosslinked to pitaya-derived nucleic acids and then tested on their antibacterial activities. These modified nanogels (NGs), characterized to be spherical, amorphous and negatively-charged, are proven to suppress bacterial growth and cause bacterial deformation. From immunoblotting results, it's found that hydrophobic groups on the benzene rings enhanced the membranolytic activity against pathogenic bacteria. Among these NGs, DNA-EV, DNA-IV and DNA-SY NGs significantly neutralized P. aeruginosa-induced lethality in C. elegans and extended their lifespan. This study shows functional groups on benzene rings enhance antibacterial activities and provides an alternative solution to drug-resistant infections.