Staphylococcal Enterotoxins Promote Virulence in Bacterial Keratitis.
Staphylococcal Enterotoxins Promote Virulence in Bacterial Keratitis.
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DOI：
10.1167/iovs.64.5.5
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发表时间：
2023-05-01
影响因子：
4.4
通讯作者：
Wozniak RAF
中科院分区：
文献类型：
--
作者：
Johnson WL;Sohn M;Woeller CF;Wozniak RAF
金黄色葡萄球菌是角膜感染（角膜炎）的重要病因。为了更好地了解介导角膜炎的毒力机制，最近的一项比较基因组学研究显示，一组分泌的肠毒素在眼部与非眼部金黄色葡萄球菌临床感染分离株中具有更高的患病率，这表明这些毒素在角膜炎中起关键作用。虽然众所周知，肠毒素可引起中毒性休克综合征和金黄色葡萄球菌食物中毒，但尚未显示肠毒素介导角膜炎的毒力。一组临床分离试验菌株，包括编码5种肠毒素（sed、sej、sek、seq、ser）的角膜炎分离株及其对应的肠毒素缺失突变株和互补株，一种不含肠毒素的角膜炎分离株，以及非眼部金黄色葡萄球菌菌株USA300及其对应的肠毒素缺失和互补株，在原发性角膜上皮模型和显微镜下评估细胞粘附、侵袭和细胞毒性。此外，在角膜炎的体内模型中评估菌株，以量化肠毒素基因表达并测量疾病严重程度。我们证明，虽然肠毒素不影响细菌的粘附或侵袭，但它们确实在体外对角膜上皮细胞产生直接的细胞毒性。在体内模型中，sed, sej, sek, seq， ser在感染72小时内具有可变的基因表达，并且编码肠毒素的测试菌株导致细菌负担增加以及宿主细胞因子反应降低。我们的结果支持葡萄球菌肠毒素在促进金黄色葡萄球菌角膜炎毒力中的新作用。
Staphylococcus aureus is an important cause of corneal infections (keratitis). To better understand the virulence mechanisms mediating keratitis, a recent comparative genomics study revealed that a set of secreted enterotoxins were found with higher prevalence among ocular versus non-ocular S. aureus clinical infection isolates, suggesting a key role for these toxins in keratitis. Although well known to cause toxic shock syndrome and S. aureus food poisoning, enterotoxins have not yet been shown to mediate virulence in keratitis. A set of clinical isolate test strains, including a keratitis isolate that encodes five enterotoxins (sed, sej, sek, seq, ser), its corresponding enterotoxin deletion mutant and complementation strain, a keratitis isolate devoid of enterotoxins, and the non-ocular S. aureus strain USA300 along with its corresponding enterotoxin deletion and complementation strains, were evaluated for cellular adhesion, invasion and cytotoxicity in a primary corneal epithelial model as well as with microscopy. Additionally, strains were evaluated in an in vivo model of keratitis to quantify enterotoxin gene expression and measure disease severity. We demonstrate that, although enterotoxins do not impact bacterial adhesion or invasion, they do elicit direct cytotoxicity in vitro toward corneal epithelial cells. In an in vivo model, sed, sej, sek, seq, ser were found to have variable gene expression across 72 hours of infection and test strains encoding enterotoxins resulted in increased bacterial burden as well as a reduced host cytokine response. Our results support a novel role for staphylococcal enterotoxins in promoting virulence in S. aureus keratitis.
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影响因子：
3.1
作者：
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通讯作者：
OCALLAGHAN, RJ
影响因子：
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作者：
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影响因子：
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3.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Foster, Timothy J.