一项研究说,来自适应寒冷的细菌的基因可能有助于抑制处于人体温度的病原体的生长。Francis Nano及其同事从来自北极地区的喜寒细菌中分离出了一些关键的基因,然后用它们取代了土拉弗朗西斯菌(Francisella tularensis)的9个基因。这种细菌病原体通常在常温下繁盛。这组科学家发现,所有这些经过测试的菌株在稍微高于室温的30摄氏度的温度下在细胞内繁殖,但是同样的菌株在这些细胞接触将近37摄氏度的温度的时候停止生长然后死亡。这组科学家把这些对温度敏感的土拉弗朗西斯菌注射到了大鼠和小鼠的较冷的身体部位。这组作者说,这种接种为这些啮齿动物提供了针对通常致命的这种细菌菌株的保护性免疫。
经过改造从而对温度敏感的蛋白质常常与未经修改的形式只相差一个氨基酸,而且可以恢复耐温属性。这组作者提出,通过利用超过100万年的进化,来自适应寒冷的北极细菌的基因可能帮助科学家开发出稳定的活疫苗或者研究可以通过温度变化加以抑制的细菌菌株。(生物谷Bioon.net)
生物谷推荐原文出处:
PNAS doi: 10.1073/pnas.1004119107
Essential genes from Arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines
Barry N. Duplantisa, Milan Osuskya, Crystal L. Schmerka, Darrell R. Rossa, Catharine M. Bosiob, and Francis E. Nanoa,1
aDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 3P6 Canada; and
bLaboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840
All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 °C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were shown to induce protective immunity after vaccination at a cool body site. About half of the genes that could be tested were unable to mutate to temperature-resistant forms at detectable levels. These results show that psychrophilic essential genes can be used to create a unique class of bacterial temperature-sensitive vaccines for important human pathogens, such as S. enterica and Mycobacterium tuberculosis.