Staphyloxanthin Biosynthesis and Virulence in Staphylococcus aureus : Emerging Opportunities for Anti-Virulence Therapy

Abstract

Staphylococcus aureus is a Gram-positive bacterium responsible for a broad spectrum of human infections. Staphyloxanthin (STX), a golden carotenoid pigment synthesized by the crtOPQMN operon, contributes to S. aureus virulence by enhancing resistance to oxidative stress and promoting immune evasion. STX functions as an antioxidant by scavenging free radicals and neutralizing reactive oxygen species, thereby helping S. aureus withstand neutrophil-mediated killing. In murine infection models, STX-producing strains form larger abscesses than pigment-deficient mutants, supporting a role for pigment production in bacterial survival and pathogenicity. Accordingly, targeting STX biosynthesis has emerged as a promising anti-virulence strategy. Several natural and synthetic compounds have been reported to inhibit STX production, reducing pigment synthesis without directly inhibiting bacterial growth and rendering bacteria more vulnerable to immune clearance. This review summarizes the genetic basis, regulation, and virulence-associated functions of STX and discusses recent advances in anti-virulence strategies that target pigment biosynthesis. These approaches may provide new therapeutic avenues for weakening antibiotic-resistant S. aureus strains while reducing direct selective pressure for resistance compared with conventional bactericidal antibiotics.

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