Fluoroquinolone Metalloantibiotics: Fighting Staphylococcus aureus Biofilms

Antimicrobial resistance (AMR) is one of the biggest public health challenges of this century. The misuse and/or overuse of antibiotics has triggered the rapid development of AMR mechanisms. Fluoroquinolones (FQs) are a broad-spectrum family of antibiotics, widely used in clinical practice. However, several AMR mechanisms against this family have been described. Our strategy to bypass this problem is their complexation with copper and 1,10-phenanthroline (phen). These stable complexes, known as CuFQphen metalloantibiotics, previously proved to be especially effective against methicillin-resistant Staphylococcus aureus (MRSA). This work aimed to characterize the interaction of CuFQphen metalloantibiotics with S. aureus membranes and to explore their antibiofilm activity with a combination of biophysical and microbiological approaches. Partition constants were assessed for metalloantibiotics in different mimetic systems of S. aureus membranes. The thermotropic profiles of the mimetic systems were studied in the absence and presence of the compounds. The antibiofilm activity of the metalloantibiotics was evaluated. The effects of the compounds on the membrane fluidity of MRSA clinical isolates were also investigated. Metalloantibiotics revealed a strong interaction with the lipidic component of the bacterial membranes, preferring cardiolipin-enriched domains. These complexes exhibited antibiofilm activity, and their presence proved to reduce the membrane fluidity of MRSA clinical isolates.