In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection.
In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection.
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DOI：
10.1371/journal.pone.0110872
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gilmore MS
中科院分区：
文献类型：
--
作者：
Sadaka A;Palmer K;Suzuki T;Gilmore MS
目的确定金黄色葡萄球菌及其codY突变体（codY是一种响应支链氨基酸的毒力和代谢基因的转录调节因子）在体外培养牛水（AH）和玻璃体（VH）中生长时的全局转录反应，并在一种新型小鼠前房（AC）感染模型中研究codY缺失对金黄色葡萄球菌毒力的影响。对于体外模型，我们分析了金黄色葡萄球菌及其codY突变体在化学定义培养基（CDM）、AH和VH中生长的差异转录组基因表达。并将该菌株接种于小鼠AC中。监测细菌生长、视网膜电图和炎症评分的变化。牛AH和VH为金黄色葡萄球菌的体外生长提供了足够的营养。转录组分析确定了CDM、AH和VH之间72个独特的开放阅读框差异调节≥10倍。在AC模型中，我们发现codY突变株和野生型菌株在体内的生长相当。感染后24小时，codY突变体感染眼睛的平均炎症评分和视网膜功能明显恶化。我们的体外牛AH和VH模型确定了眼环境中金黄色葡萄球菌可能的营养来源。体内模型表明，控制支链氨基酸的有效性在限制金黄色葡萄球菌眼内炎的严重程度方面具有治疗潜力。
To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model. For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored. Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection. Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity.
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影响因子：
3.2
作者：
Palmer, KL;Mashburn, LM;Whiteley, M
通讯作者：
Whiteley, M
影响因子：
2.4
作者：
Kowalski, Regis P.;Romanowski, Eric G.;Gordon, Y. J.
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Gordon, Y. J.
影响因子：
2.4
作者：
Mattis, D. M.;Spaulding, A. R.;Kranz, D. M.
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Kranz, D. M.
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Guédon, E;Serror, P;Delorme, C
通讯作者：
Delorme, C
影响因子：
3.9
作者：
Bertram, K. M.;Bula, D. V.;Arroyo, J. G.
通讯作者：
Arroyo, J. G.