Differential genome contents of nontypeable Haemophilus influenzae strains from adults with chronic obstructive pulmonary disease
Differential genome contents of nontypeable Haemophilus influenzae strains from adults with chronic obstructive pulmonary disease
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DOI：
10.1128/iai.01904-05
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发表时间：
2006-06-01
影响因子：
3.1
通讯作者：
Murphy, Timothy F.
中科院分区：
文献类型：
--
作者：
Fernaays, Matthew M.;Lesse, Alan J.;Murphy, Timothy F.
流感嗜血杆菌是引起儿童中耳炎和成人慢性阻塞性肺疾病(COPD)下呼吸道感染的重要原因。慢性阻塞性肺疾病患者经历周期性的恶化，这与获得新的细菌菌株有关。然而，并不是每一种压力的获得都与病情恶化有关。为了验证菌株之间的遗传差异可以解释致病潜力差异的假设，构建了一个由4992个随机的1.5-3kb的恶化菌株基因组片段组成的微阵列。使用与病情恶化相关的6个菌株以及与无症状定植相关的5个菌株进行竞争性杂交。鉴定了7个在所有5个定殖菌株中都不存在的序列，并在至少两个加重菌株中存在。其中一个这样的序列是一个以前没有报道的基因，与脑膜炎球菌免疫球蛋白A(IgA)蛋白酶基因有很高的同源性，这与以前描述的流感嗜血杆菌IgA蛋白酶基因不同。为了评估这7个序列在特征良好的流感嗜血杆菌菌株中的分布情况，用聚合酶链式反应对59株流感嗜血杆菌加重株和73株无症状定植株进行了筛选。任何单一序列的存在或缺失与COPD的恶化没有显著关联。然而，Logistic回归和亚组分析确定了与病情恶化相关的基因的存在和缺失的组合。这些结果表明，基因模式与流感嗜血杆菌菌株导致COPD加重的能力有关，支持了致病潜力的差异部分基于感染菌株之间的基因组差异，而不仅仅是宿主因素的概念。
Haemophilus influenzae is an important cause of otitis media in children and lower respiratory infection in adults with chronic obstructive pulmonary disease (COPD). Patients with COPD experience periodic exacerbations that are associated with acquisition of new bacterial strains. However, not every strain acquisition is associated with exacerbation. To test the hypothesis that genetic differences among strains account for differences in pathogenic potential, a microarray consisting of 4,992 random 1.5- to 3-kb genomic fragments of an exacerbation strain was constructed. Competitive hybridization was performed using six strains associated with exacerbation as well as five strains associated with asymptomatic colonization. Seven sequences that were absent in all five colonization strains and present in at least two exacerbation strains were identified. One such sequence was a previously unreported gene with high homology to the meningococcal immunoglobulin A (IgA) protease gene, which is distinct from the previously described H. influenzae IgA protease. To assess the distribution of the seven sequences among well-characterized strains of H. influenzae, 59 exacerbation strains and 73 asymptomatic colonization strains were screened by PCR for the presence of these sequences. The presence or absence of any single sequence was not significantly associated with exacerbations of COPD. However, logistic regression and subgroup analysis identified combinations of the presence and absence of genes that are associated with exacerbations. These results indicate that patterns of genes are associated with the ability of strains of H. influenzae to cause exacerbations of COPD, supporting the concept that differences in pathogenic potential are based in part on genomic differences among infecting strains, not merely host factors.