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                <term xml:lang="en">Cell envelope</term>
                <term xml:lang="en">Staphyloxanthin pigment</term>
                <term xml:lang="en">Cell membrane</term>
                <term xml:lang="en">Proteome</term>
                <term xml:lang="en">Infection</term>
                <term xml:lang="en">Oxidative stress</term>
                <term xml:lang="en">Virulence</term>
                <term xml:lang="en">Fatty acids</term>
                <term xml:lang="en">Lipids</term>
                <term xml:lang="en">Lipids Fatty acids Virulence Oxidative stress Infection Proteome Cell envelope Cell membrane Staphyloxanthin pigment</term>
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              <p>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 biotopes, milk and serum, shape S. aureus pathogenic properties and capacity to withstand environmental stresses. Milkversus serum-adapted bacteria show gross differences in envelope physical properties, membrane fatty acid composition and rigidity, and pigment production, and display distinct proteomic profiles.&lt;p&gt;Compared to serum, milk adaptation of S. aureus confers extreme resistance to ROS damage, pronounced antimicrobial tolerance, and accelerated killing in an insect 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.&lt;/p&gt;</p>
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