Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Infect Immun. 2020 May 20;88(6). doi: 10.1128/IAI.00100-20.
Enteroaggregative (EAEC) is an pathotype associated with diarrhea and growth faltering. EAEC virulence gene expression is controlled by the autoactivated AraC family transcriptional regulator, AggR. AggR activates transcription of a large number of virulence genes, including Aar, which in turn acts as a negative regulator of AggR itself. Aar has also been shown to affect expression of housekeeping genes, including H-NS, a global regulator that acts at multiple promoters and silences AT-rich genes (such as those in the AggR regulon). Although Aar has been shown to bind both AggR and H-NS , functional significance of these interactions has not been shown In order to dissect this regulatory network, we removed the complex interdependence of and by placing the genes under the control of titratable promoters. We measured phenotypic and genotypic changes on downstream genes in EAEC strain 042 and K-12 strain DH5α, which lacks the AggR regulon. In EAEC, we found that low expression of increases fimbrial gene expression via H-NS; however, when is more highly expressed, it acts as a negative regulator via AggR. In DH5α, affected expression of genes in some cases via H-NS and in some cases independent of H-NS. Our data support the model that Aar interacts in concert with AggR, H-NS, and possibly other regulators and that these interactions are likely to be functionally significant .
肠聚集性 （EAEC）是一种与腹泻和生长迟缓相关的 病原体。EAEC 毒力基因的表达受自动激活的 AraC 家族转录调节剂 AggR 控制。AggR 激活大量毒力基因的转录，包括 Aar，Aar 反过来又作为 AggR 自身的负调节剂。Aar 还被证明会影响包括 H-NS 在内的管家基因的表达，H-NS 是一种全局调节剂，作用于多个启动子并沉默 AT 丰富的基因（如 AggR 调节子中的基因）。尽管已经表明 Aar 可以结合 AggR 和 H-NS，但这些相互作用的功能意义尚未得到证明。为了剖析这个调控网络，我们通过将基因置于可滴定启动子的控制下，去除了 和 之间的复杂相互依存关系。我们在缺乏 AggR 调节子的 EAEC 菌株 042 和 K-12 菌株 DH5α 中测量了下游基因的表型和基因型变化。在 EAEC 中，我们发现 低表达会通过 H-NS 增加菌毛基因的表达；然而，当 表达水平更高时，它会通过 AggR 发挥负调节作用。在 DH5α 中， 在某些情况下通过 H-NS 影响基因的表达，在某些情况下则独立于 H-NS。我们的数据支持 Aar 与 AggR、H-NS 以及可能的其他调节剂协同作用的模型，并且这些相互作用可能具有功能意义。
