Defects in energy metabolism increase the susceptibility of <i>Staphylococcus aureus</i> and its small colony variants (SCVs) to <i>Staphylococcus lugdunensis</i> and lugdunin

The rise of antimicrobial resistance in <i>Staphylococcus aureus</i>, particularly small colony variants (SCVs), poses a significant clinical challenge due to their persistence and reduced susceptibility to antibiotics. <i>Staphylococcus lugdunensis</i> produces lugdunin, a potent antimicrobial compound that inhibits <i>S. aureus</i> growth. This study reveals that energy metabolism-deficient mutants and clinical SCVs exhibit increased susceptibility to lugdunin, underscoring the role of energy metabolism in bacterial defense. Furthermore, lugdunin enhances SCV susceptibility to antibiotics oxacillin and vancomycin, suggesting a potential strategy to overcome antibiotic resistance. By elucidating the link between energy metabolism and susceptibility to antimicrobial compounds, this study highlights lugdunin as a promising candidate for combating SCV-associated infections and antibiotic-resistant <i>S. aureus</i>.