一項研究說,，來自適應(yīng)寒冷的細(xì)菌的基因可能有助于抑制處于人體溫度的病原體的生長,。Francis Nano及其同事從來自北極地區(qū)的喜寒細(xì)菌中分離出了一些關(guān)鍵的基因，然后用它們?nèi)〈送晾ダ饰魉咕‵rancisella tularensis）的9個基因,。這種細(xì)菌病原體通常在常溫下繁盛,。這組科學(xué)家發(fā)現(xiàn),，所有這些經(jīng)過測試的菌株在稍微高于室溫的30攝氏度的溫度下在細(xì)胞內(nèi)繁殖,，但是同樣的菌株在這些細(xì)胞接觸將近37攝氏度的溫度的時候停止生長然后死亡,。這組科學(xué)家把這些對溫度敏感的土拉弗朗西斯菌注射到了大鼠和小鼠的較冷的身體部位。這組作者說,，這種接種為這些嚙齒動物提供了針對通常致命的這種細(xì)菌菌株的保護性免疫,。
經(jīng)過改造從而對溫度敏感的蛋白質(zhì)常常與未經(jīng)修改的形式只相差一個氨基酸，而且可以恢復(fù)耐溫屬性。這組作者提出,，通過利用超過100萬年的進化,，來自適應(yīng)寒冷的北極細(xì)菌的基因可能幫助科學(xué)家開發(fā)出穩(wěn)定的活疫苗或者研究可以通過溫度變化加以抑制的細(xì)菌菌株。(生物谷Bioon.net)
生物谷推薦原文出處：
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.
