Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis
Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis
复制标题
DOI：
10.1111/j.1462-2920.2003.00518.x
复制
发表时间：
2003-12-01
影响因子：
5.1
通讯作者：
Miller, SI
中科院分区：
文献类型：
--
作者：
Ernst, RK;D'Argenio, DA;Miller, SI
囊性纤维化(CF)患者慢性肺部感染的铜绿假单胞菌具有表型和基因多样性。利用PAO1菌株全基因组DNA芯片，对分离自6个月至8岁儿童CF和环境中的铜绿假单胞菌的基因组变异进行了研究。微阵列分析发现，20株菌株的PAO1开放阅读框中有89-97%，而38个基因岛的亚群缺失或分化。与CF相关的菌株没有特定的基因组嵌合体模式。许多嵌合区的区别在于它们的G+C含量较低；它们包含与噬菌体相关的基因或脓霉素基因；或者它们与VGR基因或tRNA基因连锁。对个别患者的连续分离株进行的微阵列和表型分析显示，在肺部进化过程中形成了两个大于100kBP的缺失。这些连续分离株中的基因丢失增加了获得脓黑素生产和损失吡喃摄取的可能性，每一个都可能具有适应意义。对单个CF患者呼吸道内铜绿假单胞菌多样性的进一步表征可能揭示共同的适应，可能是由基因丢失所介导的，这提示了新的治疗机会。
Pseudomonas aeruginosa strains from the chronic lung infections of cystic fibrosis (CF) patients are phenotypically and genotypically diverse. Using strain PAO1 whole genome DNA microarrays, we assessed the genomic variation in P. aeruginosa strains isolated from young children with CF (6 months to 8 years of age) as well as from the environment. Eighty-nine to 97% of the PAO1 open reading frames were detected in 20 strains by microarray analysis, while subsets of 38 gene islands were absent or divergent. No specific pattern of genome mosaicism defined strains associated with CF. Many mosaic regions were distinguished by their low G + C content; their inclusion of phage related or pyocin genes; or by their linkage to a vgr gene or a tRNA gene. Microarray and phenotypic analysis of sequential isolates from individual patients revealed two deletions of greater than 100 kbp formed during evolution in the lung. The gene loss in these sequential isolates raises the possibility that acquisition of pyomelanin production and loss of pyoverdin uptake each may be of adaptive significance. Further characterization of P. aeruginosa diversity within the airways of individual CF patients may reveal common adaptations, perhaps mediated by gene loss, that suggest new opportunities for therapy.