Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and is therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts factors affecting resistance to β-lactam antibiotics remains unclear. In the present study, we found an Δagr mutant strain with higher resistance to high concentrations of b-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membranes. To target these differences in fatty acid distribution and membrane composition, we applied several surfactants and found that sorbitan trioleate (Span85) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr suppression allows for MRSA to antagonize antibiotics via several changes, including constant expression of mecA, fatty acid metabolism and distribution, and biofilm thickening, resulting in a strain with higher resistance to β-lactam antibiotics.
Increased resistance of a methicillin-resistant Staphylococcus aureus Δagr mutant with modified control in fatty acid metabolism
