Coyne Michael J, Zitomersky Naamah Levy, McGuire Abigail Manson, Earl Ashlee M, Comstock Laurie E
Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
mBio. 2014 Jun 17;5(3):e01305-14. doi: 10.1128/mBio.01305-14.
The genome sequences of intestinal Bacteroidales strains reveal evidence of extensive horizontal gene transfer. In vitro studies of Bacteroides and other bacteria have addressed mechanisms of conjugative transfer and some phenotypic outcomes of these DNA acquisitions in the recipient, such as the acquisition of antibiotic resistance. However, few studies have addressed the horizontal transfer of genetic elements between bacterial species coresident in natural microbial communities, especially microbial ecosystems of humans. Here, we examine the genomes of Bacteroidales species from two human adults to identify genetic elements that were likely transferred among these Bacteroidales while they were coresident in the intestine. Using seven coresident Bacteroidales species from one individual and eight from another, we identified five large chromosomal regions, each present in a minimum of three of the coresident strains at near 100% DNA identity. These five regions are not found in any other sequenced Bacteroidetes genome at this level of identity and are likely all integrative conjugative elements (ICEs). Such highly similar and unique regions occur in only 0.4% of phylogenetically representative mock communities, providing strong evidence that these five regions were transferred between coresident strains in these subjects. In addition to the requisite proteins necessary for transfer, these elements encode proteins predicted to increase fitness, including orphan DNA methylases that may alter gene expression, fimbriae synthesis proteins that may facilitate attachment and the utilization of new substrates, putative secreted antimicrobial molecules, and a predicted type VI secretion system (T6SS), which may confer a competitive ecological advantage to these strains in their complex microbial ecosystem.
By analyzing Bacteroidales strains coresident in the gut microbiota of two human adults, we provide strong evidence for extensive interspecies and interfamily transfer of integrative conjugative elements within the intestinal microbiota of individual humans. In the recipient strain, we show that the conjugative elements themselves can be modified by the transposition of insertion sequences and retroelements from the recipient's genome, with subsequent transfer of these modified elements to other members of the microbiota. These data suggest that the genomes of our gut bacteria are substantially modified by other, coresident members of the ecosystem, resulting in highly personalized Bacteroidales strains likely unique to that individual. The genetic content of these ICEs suggests that their transfer from successful adapted members of an ecosystem confers beneficial properties to the recipient, increasing its fitness and allowing it to better compete within its particular personalized gut microbial ecosystem.
肠道拟杆菌属菌株的基因组序列揭示了广泛水平基因转移的证据。对拟杆菌属及其他细菌的体外研究探讨了接合转移机制以及这些DNA获取在受体中产生的一些表型结果，比如抗生素抗性的获得。然而，很少有研究涉及自然微生物群落中共存的细菌物种之间遗传元件的水平转移，尤其是人类的微生物生态系统。在此，我们研究了两名成年人体内拟杆菌属物种的基因组，以鉴定这些拟杆菌属在肠道中共存期间可能发生转移的遗传元件。利用来自一个个体的7种共存拟杆菌属物种和另一个个体的8种共存拟杆菌属物种，我们鉴定出5个大的染色体区域，每个区域在至少3种共存菌株中以近100%的DNA同一性存在。在这个同一性水平上，其他已测序的拟杆菌门基因组中均未发现这5个区域，它们可能都是整合性接合元件（ICE）。如此高度相似且独特的区域仅出现在0.4%的系统发育代表性模拟群落中，这有力地证明了这5个区域是在这些受试者的共存菌株之间转移的。除了转移所需的必需蛋白质外，这些元件还编码预测会提高适应性的蛋白质，包括可能改变基因表达的孤儿DNA甲基化酶、可能促进附着和新底物利用的菌毛合成蛋白、假定的分泌型抗菌分子以及预测的VI型分泌系统（T6SS），这可能赋予这些菌株在其复杂微生物生态系统中的竞争生态优势。
通过分析两名成年人体内肠道微生物群中共存的拟杆菌属菌株，我们为个体肠道微生物群中整合性接合元件的广泛种间和科间转移提供了有力证据。在受体菌株中，我们表明接合元件本身可通过受体基因组中插入序列和反转录元件的转座而被修饰，随后这些修饰后的元件会转移到微生物群的其他成员中。这些数据表明，我们肠道细菌的基因组会被生态系统中其他共存成员大量修饰，从而产生可能对该个体而言独一无二的高度个性化拟杆菌属菌株。这些ICE的遗传内容表明，它们从生态系统中成功适应的成员转移而来，赋予受体有益特性，提高其适应性，并使其能够在其特定的个性化肠道微生物生态系统中更好地竞争。
