Division of Infectious Diseases, Department of Medicine, State University of New York at Buffalo, Buffalo, New York, United States of America.
PLoS One. 2011;6(10):e25923. doi: 10.1371/journal.pone.0025923. Epub 2011 Oct 5.
Strains of nontypeable Haemophilus influenzae show enormous genetic heterogeneity and display differential virulence potential in different clinical settings. The igaB gene, which encodes a newly identified IgA protease, is more likely to be present in the genome of COPD strains of H. influenzae than in otitis media strains. Analysis of igaB and surrounding sequences in the present study showed that H. influenzae likely acquired igaB from Neisseria meningitidis and that the acquisition was accompanied by a ~20 kb genomic inversion that is present only in strains that have igaB. As part of a long running prospective study of COPD, molecular typing of H. influenzae strains identified a clonally related group of strains, a surprising observation given the genetic heterogeneity that characterizes strains of nontypeable H. influenzae. Analysis of strains by 5 independent methods (polyacrylamide gel electrophoresis, multilocus sequence typing, igaB gene sequences, P2 gene sequences, pulsed field gel electrophoresis) established the clonal relationship among the strains. Analysis of 134 independent strains collected prospectively from a cohort of adults with COPD demonstrated that ~10% belonged to the clonal group. We conclude that a clonally related group of strains of nontypeable H. influenzae that has two IgA1 protease genes (iga and igaB) is adapted for colonization and infection in COPD. This observation has important implications in understanding population dynamics of H. influenzae in human infection and in understanding virulence mechanisms specifically in the setting of COPD.
非典型流感嗜血杆菌菌株表现出巨大的遗传异质性，并在不同的临床环境中显示出不同的毒力潜力。igaB 基因编码一种新发现的 IgA 蛋白酶，在 COPD 型流感嗜血杆菌菌株的基因组中比中耳炎菌株更有可能存在。本研究中对 igaB 和周围序列的分析表明，流感嗜血杆菌可能从脑膜炎奈瑟菌获得了 igaB，并且这种获得伴随着大约 20kb 的基因组倒位，仅存在于具有 igaB 的菌株中。作为 COPD 长期前瞻性研究的一部分，对流感嗜血杆菌菌株进行分子分型鉴定出了一组克隆相关的菌株，这一观察结果令人惊讶，因为非典型流感嗜血杆菌菌株的特征就是遗传异质性。通过 5 种独立方法（聚丙烯酰胺凝胶电泳、多位点序列分型、igaB 基因序列、P2 基因序列、脉冲场凝胶电泳）对菌株进行分析，确立了菌株之间的克隆关系。对来自 COPD 成人队列的 134 株独立前瞻性采集的菌株进行分析表明，约 10%属于克隆群。我们得出结论，一种具有两个 IgA1 蛋白酶基因（iga 和 igaB）的非典型流感嗜血杆菌克隆相关菌株已适应 COPD 的定植和感染。这一观察结果对理解人类感染中流感嗜血杆菌的种群动态以及特别是在 COPD 环境中理解毒力机制具有重要意义。
