Oxacillin Coupled G-Quadruplexes as a Novel Biofilm-Specific Antibiotic for Staphylococcus aureus Biofilms

Renzo A. Fenati, Katherine Locock, Yue Qu, Amanda V. Ellis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

One of the most important traits of pathogenic microbial biofilms is their high tolerance to conventional antimicrobial agents, which is partially due to the presence of metabolically inactive and transiently resistant persister cells. Here, we use guanine-rich DNA structures known as G-quadruplexes (G4s) coupled with the β-lactam antibiotic, oxacillin (OX), and loaded with an iron-containing protoporphyrin IX (hemin), as OXG4/hemin complex biofilm-specific antibiotic agents. By coupling the OX to the G4, to form an OXG4/hemin complex, the diffusion of the OX was facilitated into the biofilm. Further, by utilizing the known oxidizing behavior (peroxidase-mimicking) of the G4/hemin complex, the entire system was found to be highly effectively against Staphylococcus aureus biofilms. By using G4 structures to penetrate biofilms, this work paves the way for an entirely new DNA-based therapy for biofilm eradication.

Original languageEnglish
Pages (from-to)3002-3008
Number of pages7
JournalACS Applied Bio Materials
Volume2
Issue number7
DOIs
Publication statusPublished - 15 Jul 2019

Keywords

  • antibiotic
  • biofilms
  • diffusion
  • G-quadruplexes
  • oxacillin
  • peroxidase-mimicking

Cite this