Lewis Derrick L, Notey Jaspreet S, Chandrayan Sanjeev K, Loder Andrew J, Lipscomb Gina L, Adams Michael W W, Kelly Robert M
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, EB-1,911 Partners Way, Raleigh, NC, 27695-7905, US.
Extremophiles. 2015 Mar;19(2):269-81. doi: 10.1007/s00792-014-0712-3. Epub 2014 Dec 4.
A mutant ('lab strain') of the hyperthermophilic archaeon Pyrococcus furiosus DSM3638 exhibited an extended exponential phase and atypical cell aggregation behavior. Genomic DNA from the mutant culture was sequenced and compared to wild-type (WT) DSM3638, revealing 145 genes with one or more insertions, deletions, or substitutions (12 silent, 33 amino acid substitutions, and 100 frame shifts). Approximately, half of the mutated genes were transposases or hypothetical proteins. The WT transcriptome revealed numerous changes in amino acid and pyrimidine biosynthesis pathways coincidental with growth phase transitions, unlike the mutant whose transcriptome reflected the observed prolonged exponential phase. Targeted gene deletions, based on frame-shifted ORFs in the mutant genome, in a genetically tractable strain of P. furiosus (COM1) could not generate the extended exponential phase behavior observed for the mutant. For example, a putative radical SAM family protein (PF2064) was the most highly up-regulated ORF (>25-fold) in the WT between exponential and stationary phase, although this ORF was unresponsive in the mutant; deletion of this gene in P. furiosus COM1 resulted in no apparent phenotype. On the other hand, frame-shifting mutations in the mutant genome negatively impacted transcription of a flagellar biosynthesis operon (PF0329-PF0338).Consequently, cells in the mutant culture lacked flagella and, unlike the WT, showed minimal evidence of exopolysaccharide-based cell aggregation in post-exponential phase. Electron microscopy of PF0331-PF0337 deletions in P. furiosus COM1 showed that absence of flagella impacted normal cell aggregation behavior and, furthermore, indicated that flagella play a key role, beyond motility, in the growth physiology of P. furiosus.
嗜热古菌激烈火球菌DSM3638的一个突变体(“实验室菌株”)表现出延长的指数生长期和非典型的细胞聚集行为。对该突变体培养物的基因组DNA进行测序,并与野生型(WT)DSM3638进行比较,发现145个基因存在一个或多个插入、缺失或替换(12个沉默突变、33个氨基酸替换和100个移码突变)。大约一半的突变基因是转座酶或假定蛋白。野生型转录组显示,氨基酸和嘧啶生物合成途径在生长阶段转变时发生了许多变化,这与突变体不同,突变体的转录组反映了观察到的延长的指数生长期。基于突变体基因组中移码的开放阅读框,在遗传上易于操作的激烈火球菌菌株(COM1)中进行靶向基因缺失,无法产生突变体中观察到的延长指数生长期行为。例如,一个假定的自由基S-腺苷甲硫氨酸家族蛋白(PF2064)是野生型在指数期和稳定期之间上调程度最高的开放阅读框(>25倍),尽管该开放阅读框在突变体中无反应;在激烈火球菌COM1中缺失该基因没有产生明显的表型。另一方面,突变体基因组中的移码突变对鞭毛生物合成操纵子(PF0329-PF0338)的转录产生了负面影响。因此,突变体培养物中的细胞缺乏鞭毛,与野生型不同,在指数期后阶段,基于胞外多糖的细胞聚集证据很少。对激烈火球菌COM1中PF0331-PF0337缺失的电子显微镜观察表明,鞭毛的缺失影响了正常的细胞聚集行为,此外,表明鞭毛在激烈火球菌的生长生理学中,除了运动性之外,还起着关键作用。