Bromophenanthrenequinones as antimicrobial and antibiofilm agents against Staphylococcus aureus

Staphylococcus aureus is a pathogen infamous for causing a multitude of infections, ranging from mild to life-threatening. Its ability to form biofilms exacerbates its pathogenicity, conferring antibiotic resistance and complicating treatments, particularly in hospital settings. To address this challenge, we investigated the efficacy of phenanthrenes against S. aureus. Among the 14 phenanthrenes tested, 2,7-dibromophenanthrenequinone (2,7-DBPQ) and 3,6-dibromophenanthrenequinone (3,6-DBPQ) showed promising results, with MICs of 20 and 50 µg/mL, respectively, and were bacteriostatic. Both compounds significantly inhibited biofilm formation in methicillin-sensitive and methicillin-resistant S. aureus strains. In addition to biofilm suppression, they markedly reduced key virulence factors, including hemolysis, extracellular lipase activity, and slime production. They also induced metabolic suppression and reactive oxygen species (ROS) generation. Notably, DBPQs exhibited synergistic effects with gentamicin and tetracycline, showing resilience against resistance development. Gene expression analysis via qRT-PCR confirmed the downregulation of biofilm- and virulence-associated genes (arlR, arlS, hla, saeR, sigB, psm-α, isaA, and nuc1). Collectively, these findings highlight the therapeutic potential of brominated analogues of phenanthrenequinones in treating biofilm-associated infections caused by S. aureus.