Regulatory networks controlling virulence in Neisseria gonorrhoeae and Neisseria meningitidis.

引起疾病的细菌通常在其细胞表面产生称为毒力决定因素的物质。这些毒力决定因素要么直接参与感染的发生，要么造成我们认为是传染病的损害。一些毒力决定因素一直在产生，而另一些只在特定条件下产生——它们的表达是受调节的。为了有针对性地开发新疫苗和治疗方法，重要的是要确定特定细菌种类产生的所有毒力决定因素，但也要知道哪些是受调节的，以及决定其表达的环境信号。同样重要的是，要知道毒性决定因素是否不断表达，因此代表了一个不变的目标。淋病奈瑟菌和脑膜炎奈瑟菌是两种重要的致病细菌，它们只感染人类并引起淋病和脑膜炎。目前正在确定这两种细菌的完整DNA序列。从这些数据的计算机分析来看，这些细菌似乎没有其他细菌中存在的特定调节系统。DNA测序数据的可用性使鉴定和研究毒力决定因素调控的另一种更系统的方法成为可能。由于淋病奈瑟菌和脑膜炎奈瑟菌中仍然存在有限的调控系统，因此对它们进行突变并确定哪些参与了毒力决定因素的调控是可行的。我们还将能够识别由每个系统调控的基因，确定调控是如何实现的，并利用这些信息来识别由同一系统控制的任何目前未知的毒力基因。由于通常存在的调控系统的数量和复杂性，以前从未对任何细菌物种进行过这样的分析。

Bacteria that cause disease produce substances called virulence determinants, often on their cell surface. These virulence determinants are either directly involved in allowing infection to take place, or cause the damage that we recognize as an infectious disease. Some virulence determinants are produced all the time, while others are only made in particular conditions - their expression is regulated. To target efforts in the development of new vaccines and treatments, it is important to identify all the virulence determinants produced by a particular bacterial species, but also to know which are regulated, and the environmental signals that determine their expression. It can be just as important to know whether a virulence determinant is constantly expressed, and therefore represents an invariant target. Neisseria gonorrhoeae and Neisseria meningitidis are two important disease-causing bacteria that exclusively infect humans and cause gonorrhoea, and meningitis. The complete DNA sequence of both of these bacteria is currently being determined. From computer analysis of these data, it appears that these bacteria have few of the specific regulatory systems that are present in other bacteria. The availability of DNA sequencing data enables an alternative and much more systematic approach to the identification and study of the regulation of virulence determinants. Because of the limited repertoire of regulatory systems still present in N. gonorrhoeae and N. meningitidis, it is feasible to mutate each and determine which are involved in regulation of virulence determinants. We will also be able to identify genes regulated by each system, determine how regulation is achieved, and use this information to identify any presently unknown virulence genes controlled by the same system. Such an analysis has never been previously achieved for any bacterial species, because of the number and complexity of the regulatory systems usually present.