The Use of Acute Immunosuppressive Therapy to Improve Antibiotic Efficacy against Intracellular Staphylococcus aureus.
The Use of Acute Immunosuppressive Therapy to Improve Antibiotic Efficacy against Intracellular Staphylococcus aureus.
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DOI：
10.1128/spectrum.00858-22
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发表时间：
2022-06-29
影响因子：
3.7
通讯作者：
Conlon, Brian P.
中科院分区：
文献类型：
--
作者：
Beam, Jenna E.;Maiocchi, Sophie;Cartaya, Ana;Rowe, Sarah E.;Bahnson, Edward S. M.;Conlon, Brian P.
金黄色葡萄球菌与宿主免疫系统之间的相互作用对抗生素的疗效有重要影响，提示靶向和调节金黄色葡萄球菌感染的免疫应答可能会提高抗生素的疗效，改善感染结局。正如我们之前所展示的，高水平的活性氧种(ROS)与M1样的促炎巨噬细胞反应相关，有效地诱导金黄色葡萄球菌对抗生素的耐受。虽然促炎免疫反应对于病原体负荷的初始控制至关重要，但最近的研究表明，巨噬细胞对抗炎反应或M2样反应的调节有助于金黄色葡萄球菌皮肤和软组织感染、关节炎和菌血症的解决。在这里，我们评估了宿主导向的免疫抑制化疗药物和抗炎药对金黄色葡萄球菌抗生素疗效的影响。重要性金黄色葡萄球菌是美国医院获得性感染的主要原因，抗生素治疗失败率很高。在金黄色葡萄球菌菌血症的实验模型中，巨噬细胞是一个重要的细胞内生态位。虽然促炎巨噬细胞反应对控制感染至关重要，但先前的研究已经发现抗生素治疗和促炎巨噬细胞反应之间存在拮抗关系。呼吸爆发时巨噬细胞产生的活性氧迫使金黄色葡萄球菌进入耐药状态，导致治疗效果不佳。在这里，我们的目标是确定宿主导向的免疫调节剂的潜力，减少活性氧的产生，以提高对细胞内金黄色葡萄球菌的抗生素效果。
Interactions between Staphylococcus aureus and the host immune system can have significant impacts on antibiotic efficacy, suggesting that targeting and modulating the immune response to S. aureus infection may improve antibiotic efficacy and improve infection outcome. As we’ve previously shown, high levels of reactive oxygen species (ROS), associated with an M1-like proinflammatory macrophage response, potently induce antibiotic tolerance in S. aureus. Although the proinflammatory immune response is critical for initial control of pathogen burden, recent studies demonstrate that modulation of the macrophage response to an anti-inflammatory, or M2-like, response facilitates resolution of established S. aureus skin and soft tissue infections, arthritis, and bacteremia. Here, we evaluated the impact of host-directed immunosuppressive chemotherapeutics and anti-inflammatory agents on antibiotic efficacy against S. aureus. IMPORTANCE Staphylococcus aureus is the leading cause of hospital-acquired infections in the United States with high rates of antibiotic treatment failure. Macrophages represent an important intracellular niche in experimental models of S. aureus bacteremia. Although a proinflammatory macrophage response is critical for controlling infection, previous studies have identified an antagonistic relationship between antibiotic treatment and the proinflammatory macrophage response. Reactive oxygen species, produced by macrophages during respiratory burst, coerce S. aureus into an antibiotic tolerant state, leading to poor treatment outcome. Here, we aimed to determine the potential of host-directed immunomodulators that reduce the production of reactive oxygen species to improve antibiotic efficacy against intracellular S. aureus.
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