Romero Claudia M, DeShazer David, Feldblyum Tamara, Ravel Jacques, Woods Donald, Kim H Stanley, Yu Yan, Ronning Catherine M, Nierman William C
The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.
BMC Genomics. 2006 Sep 5;7:228. doi: 10.1186/1471-2164-7-228.
More than 12,000 simple sequence repeats (SSRs) have been identified in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of phase variation in other pathogenic bacteria, these may function as mutable loci leading to altered protein expression or structure variation. To determine if such alterations are occurring in vivo, the genomes of various single-colony passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced from culture, a mouse, a horse, and two isolates from a single human patient, and the sequence compared to the published B. mallei ATCC 23344 genome sequence.
Forty-nine insertions and deletions (indels) were detected at SSRs in the five passaged strains, a majority of which (67.3%) were located within noncoding areas, suggesting that such regions are more tolerant of sequence alterations. Expression profiling of the two human passaged isolates compared to the strain before passage revealed alterations in the mRNA levels of multiple genes when grown in culture.
These data support the notion that genome variability upon passage is a feature of B. mallei ATCC23344, and that within a host B. mallei generates a diverse population of clones that accumulate genome sequence variation at SSR and other loci.
在鼻疽伯克霍尔德菌ATCC 23344的基因组中已鉴定出超过12,000个简单序列重复序列（SSR）。作为其他致病细菌中已证实的相变机制，这些序列可能作为可变位点，导致蛋白质表达改变或结构变异。为了确定这种改变是否在体内发生，对来自培养物、一只小鼠、一匹马的各种单菌落传代的鼻疽伯克霍尔德菌ATCC 23344分离株以及来自一名人类患者的两个分离株的基因组进行了测序，并将序列与已发表的鼻疽伯克霍尔德菌ATCC 23344基因组序列进行比较。
在五个传代菌株的SSR处检测到49个插入和缺失（indel），其中大多数（67.3%）位于非编码区域，这表明这些区域对序列改变的耐受性更强。与传代前的菌株相比，对两个人类传代分离株进行表达谱分析发现，在培养条件下生长时多个基因的mRNA水平发生了改变。
这些数据支持以下观点，即传代后的基因组变异性是鼻疽伯克霍尔德菌ATCC23344的一个特征，并且在宿主体内，鼻疽伯克霍尔德菌会产生多种克隆群体，这些群体在SSR和其他位点积累基因组序列变异。
