Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, P.O. Box 9101 (Route 224), 6500 HB Nijmegen, The Netherlands.
J Bacteriol. 2010 Jul;192(14):3574-83. doi: 10.1128/JB.00121-10. Epub 2010 May 7.
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 approximately 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.
流感嗜血杆菌是一种新兴的人类呼吸道病原体,是儿童中耳炎和成人慢性阻塞性肺疾病恶化的常见病因。在这里,我们报告了第一个完全组装和注释的流感嗜血杆菌分离株 RH4 的基因组序列,该分离株最初是从感染患者的血液中分离出来的。RH4 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。将 RH4 基因组与 ATCC 43617 基因组进行比较,证明了两株菌的基因含量高度保守。基于 16S rRNA 和多位点序列分型的计算机系统发育分析表明,RH4 属于血清抗性谱系。我们能够鉴定出几乎所有已知的流感嗜血杆菌毒力因子,并绘制了脂寡糖、肽聚糖和 IV 型菌毛生物合成途径的成员图谱。中心代谢途径的重建表明,RH4 依赖于脂肪酸和乙酸盐代谢,因为编码糖异生途径、三羧酸循环、糖质新生途径、戊糖磷酸途径非氧化分支、脂肪酸β-氧化途径和乙酸盐代谢所需酶的基因都存在。此外,还确定了与体内挑战性条件下生存相关的重要途径,如铁摄取途径、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,大约 88%的预测编码序列在体外条件下转录。总的来说,这些结果为进一步研究流感嗜血杆菌发病机制和疫苗开发奠定了基础。