Detection of Mixed Microbial Communities by Salmonella

尽管对大肠杆菌和鼠伤寒沙门氏菌进行了数十年的研究，微生物学家仍然无法确定，甚至无法令人信服地预测大肠杆菌基因组序列中超过30%的开放阅读框（orf）的功能。用纯培养物似乎无法观察到其中许多基因的功能。在自然界中，这类细菌通常不以纯培养物的形式存在，它们的遗传能力的一部分几乎肯定与“混合群落”的相互作用有关。与这一假设相一致，我们最近发现了一种鼠伤寒沙门氏菌受体，它只在混合微生物群落中被激活。发现的信号事件是通过SdiA检测n -酰基高丝氨酸内酯（AHLs），这是在鼠伤寒沙门氏菌中发现的LuxR同源物。sdiA基因也存在于大肠杆菌和克雷伯氏菌中，这表明它具有相对古老的功能。然而，真正值得注意的是，这些物种不产生SdiA检测到的配体。相反，SdiA检测的是存在于哺乳动物肠道和其他细菌产生的ahl中未表征的化合物。我们将测试肠道化合物是微生物起源的假设，并试图确定产生这些分子的物种。我们将使用微阵列来鉴定大肠杆菌和鼠伤寒沙门氏菌基因组中受SdiA响应ahl调控的部分，并表征这一信号事件的表型后果。

Despite decades of research on Escherichia coli and Salmonella typhimurium, microbiologists are still unable to assign, or even convincingly predict, functions for more than 30 percent of the open reading frames (ORFs) in the E. coli genome sequence. It seems likely that the functions of many of these genes may not be observable using pure cultures. In nature, such bacteria do not normally exist as pure cultures and a percentage of their genetic capacity is almost certainly involved with 'mixed community' interactions. Consistent with this hypothesis, we recently identified an S. typhimurium receptor that is activated only within a mixed microbial community. The signaling event discovered is the detection of N-acylhomoserine lactones (AHLs) by SdiA, a LuxR homolog found in S. typhimurium. The sdiA gene is also present in E. coli and Klebsiella spp, suggesting that it has a relatively ancient function. However, what is truly remarkable is that these species do not produce the ligands that are detected by SdiA. Instead, SdiA detects uncharacterized compounds present in mammalian intestines and AHLs produced by other species of bacteria. We will test the hypothesis that the intestinal compounds are microbial in origin and attempt to identify the species producing these molecules. We will use microarrays to identify the portions of the E. coli and S. typhimurium genomes that are regulated by SdiA in response to AHLs and characterize the phenotypic consequences of this signaling event.