背景：
金黄色葡萄球菌在慢性鼻 - 鼻窦炎（CRS）患者中具有较高的患病率，并且被认为在患有鼻息肉（CRSwNP）的CRS患者中发挥更多的致病性作用，CRS患者是CRS谱的严重形式，具有较差的手术结果。我们进行了微生物全基因组关联研究（mGWAS），以研究来自CRS患者的金黄色葡萄球菌分离株是否具有与鼻息肉（CRSwNP）或不含鼻息肉的CRS（CRSsNP）相关的特定遗传标记。

方法：
对从28名CRSsNP和30名CRSwNP患者收集的金黄色葡萄球菌分离物进行全基因组测序。采用mGWAS方法，使用大规模比较基因组学来识别我们数据集中的遗传变异。

结果：
观察到相当大的遗传变异，鉴定了> 90,000个单核苷酸多态性（SNP）位点。基于SNP和插入/去除（Indel），与CRS亚型几乎没有相关性。发现一个indel与CRSwNP显着相关并且发生在杆菌肽转运系统ATP结合蛋白的启动子区域。另外，发现高度可变的超抗原（SSL）蛋白的两种变体与每种CRS表型显着相关。与先前的研究一致，未观察到与其他毒力或抗生素抗性基因的显着关联。

结论：
据我们所知，本研究首次使用mGWAS研究微生物遗传变异对CRS表现的贡献。利用现有的最全面的全基因组分析方法，我们的结果表明CRS表型可能受金黄色葡萄球菌基因组内特定毒力机制以外的遗传因素的影响。

BACKGROUND:
Staphylococcus aureus has a high prevalence in chronic rhinosinusitis (CRS) patients and is suggested to play a more etiopathogenic role in CRS patients with nasal polyps (CRSwNP), a severe form of the CRS spectrum with poorer surgical outcomes. We performed a microbial genome-wide association study (mGWAS) to investigate whether S. aureus isolates from CRS patients have particular genetic markers associated with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP).

METHODS:
Whole genome sequencing was performed on S. aureus isolates collected from 28 CRSsNP and 30 CRSwNP patients. A mGWAS approach was employed using large-scale comparative genomics to identify genetic variation within our dataset.

RESULTS:
Considerable genetic variation was observed, with > 90,000 single nucleotide polymorphisms (SNPs) sites identified. There was little correlation with CRS subtype based on SNPs and Insertion/Delection (Indels). One indel was found to significantly correlate with CRSwNP and occurred in the promoter region of a bacitracin transport system ATP-binding protein. Additionally, two variants of the highly variable superantigen-like (SSL) proteins were found to significantly correlate with each CRS phenotype. No significant association with other virulence or antibiotic resistance genes were observed, consistent with previous studies.

CONCLUSION:
To our knowledge this study is the first to use mGWAS to investigate the contribution of microbial genetic variation to CRS presentations. Utilising the most comprehensive genome-wide analysis methods available, our results suggest that CRS phenotype may be influenced by genetic factors other than specific virulence mechanisms within the S. aureus genome.

https://www.ncbi.nlm.nih.gov/pubmed/30349419