Insights into the Staphylococcus aureus-host interface: global changes in host and pathogen gene expression in a rabbit skin infection model.

Insights into the Staphylococcus aureus-host interface: global changes in host and pathogen gene expression in a rabbit skin infection model.
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DOI:
10.1371/journal.pone.0117713
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
DeLeo FR
DeLeo FR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Malachowa N;Kobayashi SD;Sturdevant DE;Scott DP;DeLeo FR

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金黄色葡萄球菌是全球人类皮肤软组织感染(SSTI)的重要原因。值得注意的是,80%的SSTI是由金黄色葡萄球菌引起的,其中63%是∼脓肿和/或蜂窝织炎。虽然已经取得了进展,但我们对导致SSTI发病机制的宿主和病原体因素的了解还不完全。为了更全面地了解这一过程,我们监测了金黄色葡萄球菌转录组和选定的宿主促炎分子在兔皮肤感染模型脓肿形成和消退过程中的变化。在最初的24小时内,参与DNA修复、代谢物运输和新陈代谢的金黄色葡萄球菌转录本上调,这表明参与复制和细胞分裂的分子编码机制增加。编码毒力因子的基因,即分泌毒素和纤维连接蛋白和/或纤维蛋白原结合蛋白的表达也增加。在检测的宿主基因中,我们发现IL-8、IL-1β、抑癌素样蛋白、CCR1CXCR1(IL8RA)、CCL4(MIP1β)和CCL3(MIP1α)样蛋白的转录本是金黄色葡萄球菌脓肿形成过程中上调幅度最大的转录本。我们的发现为金黄色葡萄球菌SSTI的发病机制提供了更多的洞察力,包括宿主反应的时间成分。这些结果为未来的研究提供了跳板,旨在更好地了解轻度或中度SSTI如何/为什么进展为侵袭性疾病。
Staphylococcus aureus is an important cause of human skin and soft tissue infections (SSTIs) globally. Notably, 80% of all SSTIs are caused by S. aureus, of which ∼63% are abscesses and/or cellulitis. Although progress has been made, our knowledge of the host and pathogen factors that contribute to the pathogenesis of SSTIs is incomplete. To provide a more comprehensive view of this process, we monitored changes in the S. aureus transcriptome and selected host proinflammatory molecules during abscess formation and resolution in a rabbit skin infection model. Within the first 24 h, S. aureus transcripts involved in DNA repair, metabolite transport, and metabolism were up-regulated, suggesting an increase in the machinery encoding molecules involved in replication and cell division. There was also increased expression of genes encoding virulence factors, namely secreted toxins and fibronectin and/or fibrinogen-binding proteins. Of the host genes tested, we found that transcripts encoding IL-8, IL1β, oncostatin M-like, CCR1, CXCR1 (IL8RA), CCL4 (MIP-1β) and CCL3 (MIP1α)-like proteins were among the most highly up-regulated transcripts during S. aureus abscess formation. Our findings provide additional insight into the pathogenesis of S. aureus SSTIs, including a temporal component of the host response. These results serve as a springboard for future studies directed to better understand how/why mild or moderate SSTIs progress to invasive disease.
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