Badie Golnaz, Heithoff Douglas M, Mahan Michael J
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara 93106, USA.
Infect Immun. 2004 Nov;72(11):6707-10. doi: 10.1128/IAI.72.11.6707-6710.2004.
Yersinia pseudotuberculosis mutants that overproduce the DNA adenine methylase (DamOP Yersinia) are attenuated, confer robust protective immune responses, and synthesize or secrete several Yersinia outer proteins (Yops) under conditions that are nonpermissive for synthesis and secretion in wild-type strains. To understand the molecular basis of immunity elicited by DamOP Yersinia, we investigated the effects of Dam overproduction on the synthesis and localization of a principal Yersinia immunogen, LcrV, a low-calcium-responsive virulence factor involved in Yop synthesis, localization, and suppression of host inflammatory activities. Dam overproduction relaxed the stringent temperature and calcium regulation of LcrV synthesis. Moreover, the LcrV-dependent synthesis and localization of the actin cytotoxin, YopE, were shown to be relaxed in DamOP cells, suggesting that the synthesis and localization of Yops can occur via both LcrV-dependent and -independent mechanisms. Last, the immunity conferred by DamOP Yersinia was strictly dependent on the presence of LcrV, which may result from its role (i) as an immunogen, (ii) as an immunomodulator of host anti-inflammatory activities, or (iii) in the altered synthesis and localization of Yops that could contribute to immunogen repertoire expansion.
过量产生DNA腺嘌呤甲基化酶的假结核耶尔森菌突变体（DamOP耶尔森菌）毒力减弱，能引发强烈的保护性免疫反应，并且在野生型菌株中不允许合成和分泌的条件下合成或分泌几种耶尔森菌外膜蛋白（Yops）。为了了解DamOP耶尔森菌引发免疫的分子基础，我们研究了Dam过量表达对主要耶尔森菌免疫原LcrV的合成和定位的影响，LcrV是一种低钙反应性毒力因子，参与Yop的合成、定位以及对宿主炎症活性的抑制。Dam的过量表达放宽了对LcrV合成的严格温度和钙调节。此外，在DamOP细胞中，肌动蛋白细胞毒素YopE的LcrV依赖性合成和定位也表现出放宽，这表明Yops的合成和定位可以通过LcrV依赖性和非依赖性机制发生。最后，DamOP耶尔森菌赋予的免疫力严格依赖于LcrV的存在，这可能是由于其（i）作为免疫原、（ii）作为宿主抗炎活性的免疫调节剂或（iii）在Yops合成和定位改变中所起的作用，而这可能有助于免疫原库的扩展。
