Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity.
Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity.
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DOI：
10.1084/jem.20050846
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发表时间：
2005-07-18
影响因子：
15.3
通讯作者：
Nizet, Victor
中科院分区：
文献类型：
--
作者：
Liu, George Y;Essex, Anthony;Buchanan, John T;Datta, Vivekanand;Hoffman, Hal M;Bastian, John F;Fierer, Joshua;Nizet, Victor
由类胡萝卜素色素赋予的金色是人类病原体金黄色葡萄球菌的表皮特征。在这里，我们证明了这种标志性表型在毒力中的作用。与野生型（WT）细菌相比，S.具有破坏的类胡萝卜素生物合成的金黄色葡萄球菌突变体对氧化剂杀伤更敏感，具有受损的中性粒细胞存活，并且在小鼠皮下脓肿模型中致病性较低。WT S的生存优势金黄色葡萄球菌相对于类胡萝卜素缺陷型突变体在抑制嗜中性粒细胞氧化爆发后或在人或鼠烟酰胺腺嘌呤二核苷酸磷酸氧化酶缺陷型宿主中的表达丧失。相反，S.金黄色类胡萝卜素在无色素的化脓性链球菌中赋予增强的氧化剂和中性粒细胞抗性以及增加的动物毒力。封锁S。金黄色葡萄球菌的胡萝卜素生成增加了氧化剂敏感性，降低了全血存活率，提示了抗生素治疗的新靶点。
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.