Staphylococcus aureus ST398 gene expression profiling during ex vivo colonization of porcine nasal epithelium

Staphylococcus aureus is a common human and animal opportunistic pathogen. In humans nasal carriage of S. aureus is a risk factor for various infections. Methicillin-resistant S. aureus ST398 is highly prevalent in pigs in Europe and North America. The mechanism of successful pig colonization by MRSA ST398 is poorly understood. Previously, we developed a nasal colonization model of porcine nasal mucosa explants to identify molecular traits involved in nasal MRSA colonization of pigs. Here, we report the analysis of the transcriptome of MRSA ST398 strain S0462 during colonization on the explant epithelium. Major regulated genes were encoding metabolic processes and regulation of these genes represents metabolic adaptation to nasal mucosa explants. Colonization was not accompanied by significant changes in transcripts of main virulence associated genes or known human colonization factors. Here, we document regulation of two genes which have potential influence on S. aureus colonization; cysteine extracellular proteinase (scpA) and von Willebrand factor-binding protein (vwbp, located on SaPIbov5). Colonization with isogenic-deletion strains (Δvwbp and ΔscpA) did not alter the nasal S. aureus colonization compared to wild type. Our results suggest that nasal colonization with MRSA ST398 is a complex event that is accompanied with changes in bacterial gene expression regulation and metabolic adaptation. Number of the samples: 5 (timepoint 0 min, 30 min, 60 min, 90 min and 180 min) in 4 replicates. 4 control samples

金黄色葡萄球菌（Staphylococcus aureus）是一类常见的人畜机会致病菌。对人类而言，鼻腔定植该菌是引发多种感染的风险因子。耐甲氧西林金黄色葡萄球菌ST398（Methicillin-resistant S. aureus ST398）在欧洲与北美的猪群中流行率极高，但其成功定植猪鼻腔的分子机制目前仍不明晰。
此前，本研究已建立猪鼻黏膜外植体鼻腔定植模型，用于筛选参与猪鼻腔耐甲氧西林金黄色葡萄球菌定植的分子特征。本研究针对定植于外植体上皮的耐甲氧西林金黄色葡萄球菌ST398菌株S0462开展转录组（transcriptome）分析。结果显示，主要差异调控基因编码参与代谢过程的蛋白，此类基因的表达调控反映了菌株对鼻黏膜外植体的代谢适应性。本次定植过程未伴随主要毒力相关基因或已知人类定植相关基因的转录水平显著变化。
本研究明确了两个对金黄色葡萄球菌定植具有潜在影响的基因：胞外半胱氨酸蛋白酶编码基因scpA，以及血管性血友病因子结合蛋白编码基因vwbp（定位于SaPIbov5）。通过构建vwbp与scpA的同基因缺失菌株开展验证，结果显示，上述缺失菌株的鼻腔定植能力与野生型菌株相比无显著差异。
本研究结果表明，耐甲氧西林金黄色葡萄球菌ST398的鼻腔定植是一个复杂的生物学过程，伴随细菌基因表达调控与代谢适应性的改变。本研究的样本设置为：5个时间节点（0 min、30 min、60 min、90 min及180 min），每个时间点设4次生物学重复，另设4份对照样本。