Painter Kimberley L, Hall Alex, Ha Kam Pou, Edwards Andrew M
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom
Infect Immun. 2017 Nov 17;85(12). doi: 10.1128/IAI.00659-17. Print 2017 Dec.
Small-colony variants (SCVs) of typically lack a functional electron transport chain and cannot produce virulence factors such as leukocidins, hemolysins, or the antioxidant staphyloxanthin. Despite this, SCVs are associated with persistent infections of the bloodstream, bones, and prosthetic devices. The survival of SCVs in the host has been ascribed to intracellular residency, biofilm formation, and resistance to antibiotics. However, the ability of SCVs to resist host defenses is largely uncharacterized. To address this, we measured the survival of wild-type and SCV in whole human blood, which contains high numbers of neutrophils, the key defense against staphylococcal infection. Despite the loss of leukocidin production and staphyloxanthin biosynthesis, SCVs defective for heme or menaquinone biosynthesis were significantly more resistant to the oxidative burst than wild-type bacteria in human blood or the presence of purified neutrophils. Supplementation of the culture medium of the heme-auxotrophic SCV with heme, but not iron, restored growth, hemolysin and staphyloxanthin production, and sensitivity to the oxidative burst. Since is a natural heme auxotroph and cause of bloodstream infection, we explored whether restoration of the electron transport chain in this organism also affected survival in blood. Incubation of with heme increased growth and restored catalase activity but resulted in decreased survival in human blood via increased sensitivity to the oxidative burst. Therefore, the lack of functional electron transport chains in SCV and wild-type results in reduced growth rate but provides resistance to a key immune defense mechanism.
金黄色葡萄球菌的小菌落变异株（SCVs）通常缺乏功能性电子传递链，无法产生诸如白细胞毒素、溶血素或抗氧化剂葡萄球菌黄素等毒力因子。尽管如此，SCVs与血液、骨骼和假体装置的持续性感染有关。SCVs在宿主体内的存活归因于细胞内驻留、生物膜形成和对抗生素的抗性。然而，SCVs抵抗宿主防御的能力在很大程度上尚未得到充分研究。为了解决这个问题，我们测量了野生型和SCV在全血中的存活率，全血中含有大量中性粒细胞，这是对抗葡萄球菌感染的关键防御细胞。尽管白细胞毒素产生和葡萄球菌黄素生物合成丧失，但血红素或甲萘醌生物合成缺陷的SCVs在人血或纯化中性粒细胞存在的情况下，对氧化爆发的抗性明显高于野生型细菌。用血红素而非铁补充血红素营养缺陷型SCV的培养基可恢复生长、溶血素和葡萄球菌黄素的产生以及对氧化爆发的敏感性。由于[具体细菌名称]是一种天然的血红素营养缺陷型且是血流感染的病原体，我们探究了该生物体中电子传递链的恢复是否也会影响其在血液中的存活。用血红素孵育[具体细菌名称]可增加生长并恢复过氧化氢酶活性，但通过增加对氧化爆发的敏感性导致其在人血中的存活率降低。因此，SCV[具体细菌名称]和野生型[具体细菌名称]中缺乏功能性电子传递链会导致生长速率降低，但提供了对关键免疫防御机制的抗性。
