Comprehensive study on the expression of the toxin genes of Vibrio parahaemolyticus

tdh（thermostable direct hemolysin）和trh（tdh-related hemolysin）基因被认为是副溶血性弧菌的主要毒力基因。只有表现出强β型溶血的神奈川现象（KP）阳性菌株被认为是强毒株。这些菌株携带两个tdh基因（tdh 1，tdh 2）。然而，缺乏tdh基因的KP阴性菌株最近经常从亚洲的临床来源中分离出来。一些菌株被发现携带trh基因。我们也发现了与美国分离的菌株相同的趋势。许多trh阳性菌株也携带tdh基因，这些菌株中tdh的表达低于KP阳性菌株。最近，我们发现O3：K6菌株的一个新克隆引起了大流行。O3：K6株仅携带tdh基因，为KP阳性，其tdh表达水平与经典KP阳性株相似。在所有的tdh基因中，包括从KP阴性菌株中克隆的tdh 3到tdh 5基因，只有tdh 2在高水平转录，从而有助于KP，其他tdh基因在其启动子序列中有一个重要的碱基突变。当碱基改变为tdh 2基因对应的碱基时，具有启动子突变的tdh基因有助于KP，在体内选择压力下可诱导启动子一个碱基突变，因此认为KP阴性但tdh阳性的菌株具有临床意义。trh基因的转录比tdh 2基因的转录低得多。在未来的研究中，重要的是检验在一定条件下trh转录是否可以增加。

The tdh (thermostable direct hemolysin) and trh (tdh-ralated hemolysin) genes are considered major virulence genes of Vibrio parahaemolyticus. Only Kanagawa phenomenon (KP) positive strains exhibiting strong beta-type hemolysis used to be considered virulent strains. These strains carry two tdh genes (tdh1, tdh2). However, KP negative strains lacking the tdh gene has recently been isolated often from clinical sources in Asia. Some of the strains were found to carry the trh gene. We also found the same tendency with the stains isolated in the United States. Many trh-positive strains also carried the tdh gene and the tdh expression in these strains was lower than that of KP-positive strains. Very recently, we found that a new clone of the O3 : K6 strains has caused a pandemic. The O3 : K6 strains carried the tdh gene only and were KP positive, and the level of tdh expression was similar to that of classical KP-positive strains. Of all the tdh genes, including tdh3 to tdh5 genes cloned from KP-negative strains, only the tdh2 was transcribed at a high level and thus contributed to KP.The other tdh genes had one important base mutation in their promoter sequences. When the base was changed to the base corresponding to that of the tdh2 gene, the tdh genes with promoter mutation contributed to KP.The one-base promoter mutation can be induced under a selective pressure in vivo, and thus the KP-negative but tdh-positive strains are considered clinically significant. Transcription of the trh gene is much lower than that of the tdh2 gene. It is important to examine in a future study whether trh transcription can be increased under a certain condition.