Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
BMC Genomics. 2011 Jan 26;12:70. doi: 10.1186/1471-2164-12-70.
M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed.
The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement.
M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens.
粘膜炎莫拉菌是一种革兰氏阴性、γ-变形菌，是与中耳炎（OM）和慢性阻塞性肺疾病（COPD）恶化相关的机会性人类病原体。仅在美国，治疗这些疾病的直接和间接成本每年就超过 330 亿美元，而且粘膜炎莫拉菌临床分离株对β-内酰胺类抗生素几乎普遍耐药，因此需要更深入地了解这种病原体的基因组及其在分离株中的变异性。
确定并分析了 10 个地理位置和表型多样化的粘膜炎莫拉菌临床分离株以及 2 个公开可用的基因组的基因组序列。对这 12 个基因组进行了详细的比较和预测分析，旨在表征超基因组并了解该物种的代谢和致病潜力。共鉴定出 2383 个基因簇，其中 1755 个是核心基因簇，其余 628 个基因簇不均匀分布在 12 个分离株中。这些发现与分布式基因组假说（DGH）一致，该假说认为该物种的基因组拥有比任何单个分离株都多得多的基因。多次和成对的全基因组比对突出了染色体的有限重排。
尽管粘膜炎莫拉菌的基因内容和染色体组织数据支持 DGH，但总体上显示出适度的基因多样性。这些发现与该物种作为一个整体的报道的异质性以及介导 OM 和 COPD 的其他细菌病原体形成鲜明对比，为粘膜炎莫拉菌的发病机制提供了重要的见解，有助于开发新的治疗方案。
