Foulongne V, Michaux-Charachon S, Jumas-Bilak E, O'Callaghan D, Ramuz M
Inserm U431, faculté de médecine, avenue Kennedy, 30900, Nîmes, France.
Pathol Biol (Paris). 2004 Mar;52(2):104-14. doi: 10.1016/j.patbio.2003.06.001.
One of the recent preoccupations of medical microbiology has been to characterise the mechanisms of virulence of bacterial pathogens at the molecular level. One hundred years after Koch, Stanley Falkow proposed a new, molecular version of Koch's postulates to define avirulence gene: (a) the gene confers a certain phenotype to the studied bacteria, (b) inactivation of the gene abolishes the phenotype, (c)reintroduction of the gene restores the wild type to the mutant. Although this strategy, based upon mutagenesis and the use of experimental models, allows the identification of many genes, it is not comprehensive. Other methods can be used to complete the identification of virulence factors such as differential expression, either at the level of transcription (transcriptome) or at the level of protein expression (proteome). All these techniques are now supported by the data from complete genome sequencing projects. The pool of information obtained from these approaches allows the definition of the 'virulome', which is the assembly of factors a pathogen requires for virulence. Understanding the virulome will open the way to the development of new strategies for vaccination or the development of new generation of antimicrobials.
医学微生物学近来关注的一个问题是在分子水平上描述细菌病原体的毒力机制。在科赫提出其理论一百年后，斯坦利·法尔科夫提出了一个新的、分子层面的科赫法则来定义无毒力基因：（a）该基因赋予所研究细菌某种表型，（b）基因失活会消除该表型，（c）基因重新导入会使突变体恢复为野生型。尽管基于诱变和实验模型的这种策略能够鉴定出许多基因，但并不全面。还可以使用其他方法来完成毒力因子的鉴定，比如在转录水平（转录组）或蛋白质表达水平（蛋白质组）进行差异表达分析。现在，所有这些技术都得到了全基因组测序项目数据的支持。从这些方法中获得的信息库使得“毒力组”得以定义，毒力组是病原体发挥毒力所需因子的集合。了解毒力组将为开发新的疫苗接种策略或新一代抗菌药物开辟道路。
