Fernaays Matthew M, Lesse Alan J, Sethi Sanjay, Cai Xueya, Murphy Timothy F
Department of Microbiology, VA Western New York Healthcare System, Medical Research 151, 3495 Bailey Avenue, Buffalo, NY 14215, USA.
Infect Immun. 2006 Jun;74(6):3366-74. doi: 10.1128/IAI.01904-05.
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.
流感嗜血杆菌是儿童中耳炎以及慢性阻塞性肺疾病（COPD）成人患者下呼吸道感染的重要病因。COPD患者会经历周期性加重，这与新细菌菌株的获得有关。然而，并非每次菌株获得都与病情加重相关。为了验证菌株间的基因差异导致致病潜力不同这一假说，构建了一个由一株加重病情菌株的4992个随机1.5至3kb基因组片段组成的微阵列。使用六株与病情加重相关的菌株以及五株与无症状定植相关的菌株进行竞争性杂交。鉴定出了在所有五株定植菌株中均不存在且在至少两株加重病情菌株中存在的七个序列。其中一个这样的序列是一个以前未报道的基因，与脑膜炎球菌免疫球蛋白A（IgA）蛋白酶基因具有高度同源性，这与先前描述的流感嗜血杆菌IgA蛋白酶不同。为了评估这七个序列在特征明确的流感嗜血杆菌菌株中的分布情况，通过PCR对59株加重病情菌株和73株无症状定植菌株进行筛选，以检测这些序列的存在情况。任何单个序列的存在与否与COPD病情加重均无显著相关性。然而，逻辑回归和亚组分析确定了基因存在和缺失的组合与病情加重相关。这些结果表明，基因模式与流感嗜血杆菌菌株导致COPD病情加重的能力相关，支持了致病潜力差异部分基于感染菌株间基因组差异而非仅仅宿主因素的观点。
