| Autor: |
Chen A; Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA., Dellos-Nolan S; Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA., Lu Y; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA., West JS; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA., Wozniak DJ; Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.; Department of Microbiology, College of Arts and Sciences, The Ohio State University, Columbus, Ohio, USA., Mitton-Fry MJ; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA. |
| Abstrakt: |
The development of novel treatments for Staphylococcus aureus infections remains a high priority worldwide. We previously reported compounds 0147 and 0186, novel bacterial topoisomerase inhibitors (NBTIs) with potent antibacterial activity against S. aureus, including methicillin-resistant S. aureus. Here, we further investigated the in vitro activity of 0147 and 0186 against S. aureus ATCC 29213. Both compounds demonstrated bactericidal activity against planktonic and biofilm S. aureus, which then translated into significant inhibition of biofilm formation. Combinations of NBTIs and glycopeptides yielded indifferent interactions against planktonic S. aureus, but several had synergistic effects against S. aureus biofilms. This work reinforces the potential of NBTIs as future therapeutics for S. aureus infections. IMPORTANCE The pathogen Staphylococcus aureus contributes substantially to infection-related mortality. Biofilms render bacteria more recalcitrant to antibacterial therapy. The manuscript describes the potent activity of a new class of antibacterial agents against both planktonic and biofilm populations of Staphylococcus aureus. |
