DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?
DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?
复制标题
DOI：
10.1007/s10096-016-2663-3
复制
发表时间：
2016-08-01
影响因子：
4.5
通讯作者：
Bjornholt, J. V.
中科院分区：
文献类型：
--
作者：
Blomfeldt, A.;Aamot, H. V.;Bjornholt, J. V.
由于微生物-宿主的复杂和动态相互作用，提供微生物遗传决定因素对金黄色葡萄球菌血流感染(SABSI)预后影响的证据是具有挑战性的。我们最近的基于人群的前瞻性研究报告了金黄色葡萄球菌克隆复合体(CC)30基因与SABSI患者死亡率之间的关联。这项后续调查的目的是检查SABSI分离株的基因图谱，并测试金黄色葡萄球菌特定遗传特征与死亡率相关的假设。对305株SABSI菌株和38株无症状鼻携带者的金黄色葡萄球菌CC30菌株进行了DNA芯片分析和spA分型。Fisher‘s精确检验、最小绝对收缩和选择算子(套索)和弹性净回归被用来区分由患者结果和特征定义的四组。没有发现特定的金黄色葡萄球菌基因决定因素与SABSI患者的死亡率有关。应用套索回归和弹性网络回归分析发现，与非CC30菌株相比，agrIII和CnA与金黄色葡萄球菌CC30呈正相关，SETC(=selX)和seh与金黄色葡萄球菌CC30呈负相关。编码免疫逃避分子的基因Chp和sak在CC30 SABSI分离株中的出现频率高于CC30携带者分离株，表明其毒力潜力更高。总之，通过DNA微阵列分析和最先进的统计分析，没有发现特定的金黄色葡萄球菌基因与死亡率有关。下一个自然的步骤是用更高分辨率的方法在更大的样本中检验这一假设，比如全基因组测序。
Providing evidence for microbial genetic determinants' impact on outcome in Staphylococcus aureus bloodstream infections (SABSI) is challenging due to the complex and dynamic microbe-host interaction. Our recent population-based prospective study reported an association between the S. aureus clonal complex (CC) 30 genotype and mortality in SABSI patients. This follow-up investigation aimed to examine the genetic profiles of the SABSI isolates and test the hypothesis that specific genetic characteristics in S. aureus are associated with mortality. SABSI isolates (n = 305) and S. aureus CC30 isolates from asymptomatic nasal carriers (n = 38) were characterised by DNA microarray analysis and spa typing. Fisher's exact test, least absolute shrinkage and selection operator (LASSO) and elastic net regressions were performed to discern within four groups defined by patient outcome and characteristics. No specific S. aureus genetic determinants were found to be associated with mortality in SABSI patients. By applying LASSO and elastic net regressions, we found evidence suggesting that agrIII and cna were positively and setC (=selX) and seh were negatively associated with S. aureus CC30 versus non-CC30 isolates. The genes chp and sak, encoding immune evasion molecules, were found in higher frequencies in CC30 SABSI isolates compared to CC30 carrier isolates, indicating a higher virulence potential. In conclusion, no specific S. aureus genes were found to be associated with mortality by DNA microarray analysis and state-of-the-art statistical analyses. The next natural step is to test the hypothesis in larger samples with higher resolution methods, like whole genome sequencing.