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几十年的研究，但微生物学家仍然无法指定，甚至令人信服地预测，大肠杆菌基因组序列中30%以上的开放阅读框(ORF)的功能。这些基因中的许多功能似乎很可能在纯培养中是观察不到的。在自然界中，这种细菌通常不作为纯培养物存在，它们的遗传能力的一定比例几乎肯定与“混合群落”的相互作用有关。与这一假设一致，我们最近发现了一种仅在混合微生物群落中激活的鼠伤寒沙门氏菌受体。发现的信号事件是SdiA检测到N-酰基高丝氨酸内酯(AHLS)，SdiA是在鼠伤寒沙门氏菌中发现的LuxR同源物。在大肠杆菌和克雷伯氏菌中也存在sdiA基因，这表明它具有相对古老的功能。然而，真正值得注意的是，这些物种不会产生SdiA检测到的配体。相反，SdiA检测到哺乳动物肠道中存在的未知化合物和其他种类细菌产生的AHL。我们将检验肠道化合物起源于微生物的假设，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受SdiA调控的部分大肠杆菌和鼠伤寒沙门氏菌基因组，以响应AHLS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.