The challenge of new drug discovery for tuberculosis

Tuberculosis (TB) is more prevalent in the world today than at any other time in human history. Mycobacterium tuberculosis, the pathogen responsible for TB, uses diverse strategies to survive in a variety of host lesions and to evade immune surveillance. A key question is how robust are our approaches to discovering new TB drugs, and what measures could be taken to reduce the long and protracted clinical development of new drugs. The emergence of multi-drug-resistant strains of M. tuberculosis makes the discovery of new molecular scaffolds a priority, and the current situation even necessitates the re-engineering and repositioning of some old drug families to achieve effective control. Whatever the strategy used, success will depend largely on our proper understanding of the complex interactions between the pathogen and its human host. In this review, we discuss innovations in TB drug discovery and evolving strategies to bring newer agents more quickly to patients.     

统筹区域发展中不可忽视的特殊生态系统--自然疫源地与自然疫源性疾病

在我国如此广阔的地域,极其多样性的经济、社会和自然环境条件下统筹区域发展和进行区域合作开发自然资源时,应密切关注在不同自然景观中可能潜在着某种由病原生物、宿主动物和媒介生物所形成的特殊生态系统——自然资疫地与自然疫源性疾病,对此应加强调研和防治,以保障统筹区域的可持续发展和区域合作的顺利。     

烟草赤星病菌孢子萌发和侵染条件的研究

用烟草赤星病菌两个菌株进行测定,孢子在烟草叶面萌发能力最强;其次是在1％的葡萄糖溶液中;在蒸馏水中萌发最弱。在侵染试验中,用丙酮和70％酒精清洗的幼苗叶片发病加重;露天放置的烟苗较生长在温室内的烟苗发病重。在3种接种方法中,以孢子悬滴法效果最好。侵染和接种方法中的幼苗,其叶面微生物在种类和数量上均以处理的不同而有差别。     

The potential role of pathogens in biological control

It is now well established that pathogens such as viruses, fungi bacteria and protozoans can have profound effects on the dynamics of their invertebrate host populations. Theoretical models of invertebrate host-pathogen interactions which assume uniform structure of the pathogen population may reasonably explain the oscillatory behaviour observed in some systems, but do not adequately describe the existence of more constant populations found in other host-pathogen interactions. An examination of the literature relating to these relatively stable systems suggests that the common thread is the eventual transmission of some of the more protected, longer-lived stages of the pathogen occurring in reservoirs, such as the soil, host cadavers on trees, or the live host itself. In this letter, I propose a new theoretical model which incorporates this population structure and accounts for the range of dynamics observed in natural systems. In particular, I show that host populations may be regulated to low and relatively constant densities if sufficient numbers of pathogens are trans-located from pathogen reservoirs to habitats where transmission can occur. An understanding of pathogen reservoirs may be of value in the design of biological control programmes and may greatly increase the effectiveness of pathogens as biological control agents.     

Widespread distribution and fitness contribution of Xanthomonas campestris avirulence gene avrBs2

Disease-resistance genes introduced into cultivated plants are often rendered ineffective by the ability of pathogen populations to overcome host resistance. The bacterial pathogen Xanthomonas campestris pathovar vesicatoria causes bacterial spot disease of tomato and pepper, and this pathogen has been shown to overcome disease resistance in pepper (Capsicum annuum) by evading the recognition and defence response of the host plant. Numerous resistance genes to bacterial spot have been identified in pepper and its wild relatives, each providing resistance to specific races of X.c. vesicatoria. The resistance gene Bs1, for example, provides resistance to X.c. vesicatoria strains expressing the avirulence gene avrBs1; Bs2 provides resistance to stains expressing avrBs2 and so on. We now report that avr Bs2 is highly conserved among strains of X.c. vesicatoria, and among many other pathovars of X. campestris. Furthermore, we find that avrBs2 is in fact needed for full virulence of the pathogen on susceptible hosts. This implies that plants carrying Bs2 can recognize an essential gene of the bacterial pathogen, which may explain why Bs2 confers the only effective field resistance to X.c. vesicatoria in pepper.     

由两种彼此完全交叉免疫的病毒导致的流行病模型

研究了一类带有竞争性的双致病毒的SIRS流行病模型,在假定完全交叉免疫和密度依赖死亡率的条件下得到了病毒间排他性的条件及疾病持续的条件.     

油桐枯萎病病原菌的研究

<正>作者在油桐枯萎病病原菌的分离、鉴定、寄主范围及生物学特性等方面作了研究,认为:从其形态特征看,应属尖孢镰刀菌,从寄主范围看,未发现此菌为害其它寄主植物,尖孢镰刀菌的其它专化型和茄病镰刀菌(Fusarium solani)也很少为害油桐。作者建议将油桐枯萎病病原菌命名为尖孢镰刀菌油桐专化型(Fusurium oxysporum Sehl.f.Sp.aleuritidis f.Sp.nov)。 油桐枯萎病病原菌孢子能在pH 3—12范围内的清水中正常萌芽。相对湿度低于80％孢子不能萌芽。孢子萌芽的最适温度为25—30℃。病原菌生长对碳,氮,磷素无特殊要求,但氮素为     

Imperfect vaccines and the evolution of pathogen virulence.

Vaccines rarely provide full protection from disease. Nevertheless, partially effective (imperfect) vaccines may be used to protect both individuals and whole populations. We studied the potential impact of different types of imperfect vaccines on the evolution of pathogen virulence (induced host mortality) and the consequences for public health. Here we show that vaccines designed to reduce pathogen growth rate and/or toxicity diminish selection against virulent pathogens. The subsequent evolution leads to higher levels of intrinsic virulence and hence to more severe disease in unvaccinated individuals. This evolution can erode any population-wide benefits such that overall mortality rates are unaffected, or even increase, with the level of vaccination coverage. In contrast, infection-blocking vaccines induce no such effects, and can even select for lower virulence. These findings have policy implications for the development and use of vaccines that are not expected to provide full immunity, such as candidate vaccines for malaria.     

毛竹枯梢病病原菌竹喙球菌风险性分析

参照国际上有害生物风险性分析(Pest Risk Analysis，简称PRA)方法，从有害生物的国内分布、潜在的经济和生态环境危害性、定殖与扩散的可能性、风险管理难度以及毛竹的经济、生态、社会重要性等几个方面进行定性和定量分析，对毛竹枯梢病病原菌竹喙球菌的风险性作了综合评价。结果表明，竹喙球菌是接近于高度危险的林业有害生物，对我国竹林资源与竹业发展具有潜在的严重．威胁，应加强风险性管理力度。     

普通棉耳狨猴中乙型流感病毒的分离和鉴定

乙型流感病毒是引起人类局部流行性感冒的重要病原体，其起源和自然储存宿主目前仍不清楚。1999年夏季在某动物中心饲养的普通棉耳绒猴（Callithrix jacchus）群体中爆发了以呼吸道症状为主的急性传染病，死亡比率高达1／3。通过对死亡狨猴肺组织匀浆接种鸡胚和MDCK细胞的分离培养，分离出病毒。双份血清的红细胞凝集抑制试验证实，此分离株为此次狨猴群体感染流行的病原体。通过甲型和乙型流感病毒标准血清鉴定，证实该分离株为乙型流感病毒，命名为B/marmoset/China/1/99。