必特霉素基因工程菌航天育种的研究

探讨航天技术对必特霉素基因工程菌的育种效果。我国返回式搭载卫星对基因工程必特霉素菌种进行了航天育种，共搭载4个菌株以沙土、甘油、斜面等不同方式，经受航天环境条件处理后计算其孢子存活率、营养缺陷型出现率及菌株的发酵效价。在本实验条件下菌株的存活率均很低，尤其是沙土方式的致死率为100％，甘油及斜面孢子的致死率分别为99．79％～100％和99．81％～100％。营养缺陷型出现率为1．65％。存活菌株的负突变率高于正突变率。经筛选从408株正突变株获得了发酵效价提高11．3％～14．5％的菌株。航天技术有可能应用于基因工程必特霉素的育种，但适于其育种的空间条件必须经过详尽而细致的研究和控制。     

Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

Abstract

Gain of “antimicrobial resistance” and “adaptive virulence” has been the dominant view of Pseudomonas aeruginosa (Pa) in cystic fibrosis (CF) in the progressively damaged host airway over the course of this chronic infection. However, the pathogenic effects of CF airway-adapted Pa strains are notably reduced. We propose that CF Pa and other bacterial cohabitants undergo host adaptation which resembles the changes found in bacterial symbionts in animal hosts. Development of clonally selected and intraspecific isogenic Pa strains which display divergent colony morphology, growth rate, auxotrophy, and antibiotic susceptibility in vitro suggests an adaptive sequence of infective exploitation-parasitism-symbiotic evolution driven by host defenses. Most importantly, the emergence of CF pseudomonal auxotrophy is frequently associated with a few specific amino acids. The selective retention or loss of specific amino acid biosynthesis in CF-adapted Pa reflects bacterium-host symbiosis and coevolution during chronic infection, not nutrient availability. This principle also argues against the long-standing concept of dietary availability leading to evolution of essential amino acid requirements in humans. A novel model of pseudomonal adaptation through multicellular bacterial syntrophy is proposed to explain early events in bacterial gene decay and decreased (not increased) virulence due to symbiotic response to host defense.     

The Saccharomyces cerevisiae HIS3 and LYS2 genes complement the Schizosaccharomyces pombe his5-303 and lys1-131 mutations,respectively: new selectable markers and new multi-purpose multicopy shuttle vectors,pSP3 and pSP4

Three new S. pombe plasmids are described. Plasmids pSP3 and pSP4 are two Schizosaccharomyces pombe ars1 multicopy vectors with the Saccharomyces cerevisiae HIS3 or LYS2 genes as selectable markers. They complement the S. pombe his5-303 or lys1-131 mutations, respectively. Plasmid pSPars1 is a vector carrying the S. pombe ars1 and a unique NdeI site which allows the introduction of any selectable marker therefore bringing a unified vector backbone for the construction of new S. pombe/S. cerevisiae/E. coli shuttle vectors. These plasmids permit classical molecular genetic techniques to be performed directly.     

Metabolic pathways of L-arginine and therapeutic consequences in tumors

Difference in the metabolism of normal and cancer cells inspires to search for new, more specific and less toxic therapies than those currently used.The development of tumors is conditioned by genetic changes in cancer-transformed cells, immunological tolerance and immunosuppression. At the initial stages of carcinogenesis, the immune system shows anti-tumor activity, however later, cancer disrupts the function of Th1/Th17/Th2 lymphocytes by regulatory T (Treg) cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) and finally causes immunosuppression.Recently, much attention has been devoted to the influence of l-arginine metabolism disorders on both carcinogenesis and the immune system. l-Arginine is essential for the maturation of the T cell receptor zeta (TCRζ), and its absence deprives T-cells of the ability to interact with tumor antigens. MDSCs deplete l-arginine due to a high expression of arginase 1 (ARG1) and their number increases 4–10 times depending on the type of the cancer.L-Arginine has been shown to be essential for the survival and progression of arginine auxotrophic tumors. However, the progression of arginine non-auxotrophic tumors is independent of exogenous l-arginine, because these tumors have arginine-succinate synthetase (ASS1) activity and are available to produce l-arginine from citrulline.Clinical studies have confirmed the high efficacy of arginine auxotrophic tumors therapy based on the elimination of l-arginine. However, l-arginine supplementation may improve the results of treatment of patients with arginine non-auxotrophic cancer.This review is an attempt to explain the seemingly contradictory results of oncological therapies based on the deprivation or supplementation of l-arginine.