Felsheim Roderick F, Herron Michael J, Nelson Curtis M, Burkhardt Nicole Y, Barbet Anthony F, Kurtti Timothy J, Munderloh Ulrike G
Department of Entomology, University of Minnesota, St. Paul, MN 55108, USA.
BMC Biotechnol. 2006 Oct 31;6:42. doi: 10.1186/1472-6750-6-42.
Tick-borne pathogens cause emerging zoonoses, and include fastidious organisms such as Anaplasma phagocytophilum. Because of their obligate intracellular nature, methods for mutagenesis and transformation have not been available.
To facilitate genetic manipulation, we transformed A. phagocytophilum (Ap) to express a green fluorescent protein (GFP) with the Himar1 transposase system and selection with the clinically irrelevant antibiotic spectinomycin.
These transformed bacteria (GFP/Ap) grow at normal rates and are brightly fluorescent in human, monkey, and tick cell culture. Molecular characterization of the GFP/Ap genomic DNA confirmed transposition and the flanking genomic insertion locations were sequenced. Three mice inoculated with GFP/Ap by intraperitoneal injection became infected as demonstrated by the appearance of morulae in a peripheral blood neutrophil and re-isolation of the bacteria in culture.
蜱传病原体可引发新出现的人畜共患病,其中包括嗜吞噬细胞无形体等苛求菌。由于其专性细胞内寄生的特性,此前尚无诱变和转化方法。
为便于进行基因操作,我们利用Himar1转座酶系统将嗜吞噬细胞无形体(Ap)进行转化,使其表达绿色荧光蛋白(GFP),并选用临床不相关抗生素壮观霉素进行筛选。
这些转化后的细菌(GFP/Ap)以正常速率生长,在人、猴和蜱细胞培养物中发出明亮荧光。对GFP/Ap基因组DNA的分子特征分析证实了转座,并对侧翼基因组插入位置进行了测序。通过腹腔注射接种GFP/Ap的三只小鼠受到感染,外周血中性粒细胞中出现桑葚体以及在培养物中重新分离出细菌即证明了这一点。