Wagner Trevor K, Mulks Martha H
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
FEMS Immunol Med Microbiol. 2006 Nov;48(2):192-204. doi: 10.1111/j.1574-695X.2006.00147.x.
Actinobacillus pleuropneumoniae is the causative agent of a necrotizing hemorrhagic pleuropneumonia in swine. In this study, we investigate the possibility that the limitation of branched-chain amino acids is a stimulus that A. pleuropneumoniae will encounter during infection and will respond to by up-regulation of genes involved in branched-chain amino acid biosynthesis and virulence. Actinobacillus pleuropneumoniae genetic loci that are specifically induced during infection were screened in vitro for expression in response to limitation of branched-chain amino acids. Of 32 in vivo induced promoter clones screened in vitro, eight were induced on chemically defined medium without isoleucine, leucine and valine as compared to complete chemically defined medium. We identify the genomic context of each clone and discuss its relevance to branched-chain amino acid limitation and virulence. We conclude that limitation of branched-chain amino acids is a cue for expression of a subset in vivo induced genes, including not only genes involved in the biosynthesis of branched-chain amino acids, but also other genes that are induced during infection of the natural host. These results suggest that limitation of branched-chain amino acids may be one of an array of environmental cues responsible for the induction of virulence-associated genes in A. pleuropneumoniae.
胸膜肺炎放线杆菌是猪坏死性出血性胸膜肺炎的病原体。在本研究中，我们探究了支链氨基酸受限是否是胸膜肺炎放线杆菌在感染过程中会遇到的一种刺激因素，以及该菌是否会通过上调参与支链氨基酸生物合成和毒力的基因来作出反应。我们在体外筛选了感染过程中特异性诱导的胸膜肺炎放线杆菌基因座，以检测其对支链氨基酸受限的表达响应。在体外筛选的32个体内诱导启动子克隆中，与完全化学限定培养基相比，有8个在不含异亮氨酸、亮氨酸和缬氨酸的化学限定培养基上被诱导。我们确定了每个克隆的基因组背景，并讨论了其与支链氨基酸受限和毒力的相关性。我们得出结论，支链氨基酸受限是体内诱导基因子集表达的一个信号，这些基因不仅包括参与支链氨基酸生物合成的基因，还包括在天然宿主感染期间被诱导的其他基因。这些结果表明，支链氨基酸受限可能是导致胸膜肺炎放线杆菌毒力相关基因诱导的一系列环境信号之一。
