Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity.
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.
Liu
George Y
GY
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
Essex
Anthony
A
Buchanan
John T
JT
Datta
Vivekanand
V
Hoffman
Hal M
HM
Bastian
John F
JF
Fierer
Joshua
J
Nizet
Victor
V
D000038:Abscess / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000293:Adolescent; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002338:Carotenoids / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
D000975:Antioxidants; D002338:Carotenoids