Do fluoroquinolones disrupt bacterial membranes through chelation? This study investigates the interaction of fluoroquinolones, specifically ciprofloxacin and moxifloxacin, with bacterial lipopolysaccharides (LPS) to understand their mechanism of action. It challenges the hypothesis that fluoroquinolones' antibacterial effect stems from chelating with divalent cations, thus perturbing the integrity of the outer membrane (OM) of gram-negative bacteria. Employing biophysical techniques, the researchers examined the interaction of fluoroquinolones with whole bacteria and isolated LPS from various rough mutant strains of *Salmonella enterica* in the presence and absence of Mg2+. They found that the fluoroquinolones did not disrupt the OM's integrity. Also, they were neither incorporated into LPS monolayers nor displaced Ca2+ from LPS monolayers. The findings suggest that chelation of fluoroquinolones with divalent cations does not significantly contribute to their antibacterial effect. This research prompts a re-evaluation of the mechanisms underlying fluoroquinolone activity and potentially guides the development of new antibacterial strategies.
Published in Antimicrobial Agents and Chemotherapy, a leading journal in its field, this paper provides valuable insights into the mechanism of action of antimicrobial drugs. It helps advance the understanding of how these agents combat bacterial infections.