Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
Microbiology (Reading). 2019 Sep;165(9):917-928. doi: 10.1099/mic.0.000805. Epub 2019 Apr 17.
Phase-variable DNA methyltransferases control the expression of multiple genes via epigenetic mechanisms in a wide variety of bacterial species. These systems are called phasevarions, for phase-variable regulons. Phasevarions regulate genes involved in pathogenesis, host adaptation and antibiotic resistance. Many human-adapted bacterial pathogens contain phasevarions. These include leading causes of morbidity and mortality worldwide, such as non-typeable , and spp. Phase-variable methyltransferases and phasevarions have also been discovered in environmental organisms and veterinary pathogens. The existence of many different examples suggests that phasevarions have evolved multiple times as a contingency strategy in the bacterial domain, controlling phenotypes that are important in adapting to environmental change. Many of the organisms that contain phasevarions have existing or emerging drug resistance. Vaccines may therefore represent the best and most cost-effective tool to prevent disease caused by these organisms. However, many phasevarions also control the expression of current and putative vaccine candidates; variable expression of antigens could lead to immune evasion, meaning that vaccines designed using these targets become ineffective. It is therefore essential to characterize phasevarions in order to determine an organism's stably expressed antigenic repertoire, and rationally design broadly effective vaccines.
相变型 DNA 甲基转移酶通过表观遗传机制在多种细菌物种中控制多个基因的表达。这些系统被称为相变型调控子，用于相变型调控。相变型调控子调节与发病机制、宿主适应和抗生素耐药性相关的基因。许多适应人类的细菌病原体含有相变型调控子。这些病原体包括全球发病率和死亡率的主要原因，如非定型 和 spp。相变型甲基转移酶和相变型调控子也在环境生物和兽医病原体中被发现。许多不同的例子表明，相变型作为细菌域中的一种应急策略已经进化了多次，控制着适应环境变化的重要表型。许多含有相变型调控子的生物体具有现有的或新出现的耐药性。因此，疫苗可能是预防这些生物体引起的疾病的最佳和最具成本效益的工具。然而，许多相变型调控子也控制着当前和潜在疫苗候选物的表达；抗原的可变表达可能导致免疫逃避，这意味着使用这些靶标设计的疫苗变得无效。因此，为了确定生物体稳定表达的抗原库，并合理设计广泛有效的疫苗，对相变型调控子进行特征分析是至关重要的。
