Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen
Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen
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DOI：
10.1128/jb.00121-10
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发表时间：
2010-07-01
影响因子：
3.2
通讯作者：
Bootsma, Hester J.
中科院分区：
文献类型：
--
作者：
de Vries, Stefan P. W.;van Hijum, Sacha A. F. T.;Bootsma, Hester J.
卡他莫拉氏菌是一种新出现的人类限制性呼吸道病原体，是儿童中耳炎和成人慢性阻塞性肺疾病恶化的常见原因。在这里，我们报告了第一个完整的组装和注释的基因组序列的分离M。卡他菌，菌株RH 4，其最初分离自感染患者的血液。RH 4基因组由1，863，286个核苷酸组成，形成1，886个蛋白质编码基因。RH 4基因组与ATCC 43617重叠群的比较表明，两种菌株的基因内容是高度保守的。基于16 S rRNA和多位点序列分型的计算机系统发育分析显示，RH 4属于血清抗性谱系。我们能够识别几乎所有已知的M。卡他菌毒力因子，并绘制了脂寡糖、肽聚糖和IV型皮利的生物合成途径的成员。中心代谢途径的重建表明，RH 4依赖于脂肪酸和乙酸代谢，因为存在编码乙醛酸途径、三羧酸循环、产酸途径、戊糖磷酸途径的非氧化分支、脂肪酸的β-氧化途径和乙酸代谢所需的酶的基因。此外，还确定了在具有挑战性的体内条件下生存的重要途径，如铁获取途径、氮代谢和氧化应激反应。最后，我们通过微阵列表达谱分析表明，在体外条件下，预测的编码序列中有88%被转录。这些结果为进一步研究M.卡他病的发病机制和疫苗开发。
Moraxella catarrhalis is an emerging human-restricted respiratory tract pathogen that is a common cause of childhood otitis media and exacerbations of chronic obstructive pulmonary disease in adults. Here, we report the first completely assembled and annotated genome sequence of an isolate of M. catarrhalis, strain RH4, which originally was isolated from blood of an infected patient. The RH4 genome consists of 1,863,286 nucleotides that form 1,886 protein-encoding genes. Comparison of the RH4 genome to the ATCC 43617 contigs demonstrated that the gene content of both strains is highly conserved. In silico phylogenetic analyses based on both 16S rRNA and multilocus sequence typing revealed that RH4 belongs to the seroresistant lineage. We were able to identify almost the entire repertoire of known M. catarrhalis virulence factors and mapped the members of the biosynthetic pathways for lipooligosaccharide, peptidoglycan, and type IV pili. Reconstruction of the central metabolic pathways suggested that RH4 relies on fatty acid and acetate metabolism, as the genes encoding the enzymes required for the glyoxylate pathway, the tricarboxylic acid cycle, the gluconeogenic pathway, the nonoxidative branch of the pentose phosphate pathway, the beta-oxidation pathway of fatty acids, and acetate metabolism were present. Moreover, pathways important for survival under challenging in vivo conditions, such as the iron-acquisition pathways, nitrogen metabolism, and oxidative stress responses, were identified. Finally, we showed by microarray expression profiling that similar to 88% of the predicted coding sequences are transcribed under in vitro conditions. Overall, these results provide a foundation for future research into the mechanisms of M. catarrhalis pathogenesis and vaccine development.