Biotope-dependent resistance to reactive oxygen species, antibiotic tolerance, and virulence of Staphylococcus aureus

Abstract The human and livestock pathogen Staphylococcus aureus poses a major clinical challenge due to antibiotic treatment failure. Its resilience is mainly attributed to antibiotic resistance and tolerance mechanisms related to persistence. Here we investigate how two infection-relevant conditions, milk and serum, shape S. aureus pathogenic properties and capacity to withstand environmental stresses. Milk- versus serum-grown bacteria show gross differences in envelope physical properties, membrane fatty acid composition and rigidity, and pigment production, and display distinct proteomic profiles. Compared to growth in serum, S. aureus grown in milk exhibits extreme resistance to ROS damage, marked antimicrobial tolerance, and accelerated killing in a larval infection model. High level S. aureus pigmentation in whole milk is stimulated by milk lipids, and is responsible for high ROS resistance. The remarkable robustness of S. aureus in a milk biotope may signal the need to adjust antibiotic regimens when treating mastitis infections in humans and livestock.