<i>Staphylococcus aureus</i> golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity

TLDR

Staphylococcus aureus is distinguished by a golden pigment produced by carotenoid pigments. This study examines whether the carotenoid pigment contributes to the bacterium’s virulence. The pigment‑deficient mutant is more susceptible to oxidants, neutrophil killing, and mouse abscess formation, and its survival advantage disappears when neutrophil oxidative burst is inhibited or in NADPH oxidase‑deficient hosts, while heterologous pigment expression in Streptococcus pyogenes enhances resistance and virulence, suggesting that inhibiting carotenogenesis could be a novel therapeutic approach.

Abstract

Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase–deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy.