Functional characterization of the antibiotic resistance reservoir in the human microflora
Functional characterization of the antibiotic resistance reservoir in the human microflora
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DOI：
10.4161/viru.1.4.12010
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发表时间：
2010-07-01
期刊：
影响因子：
5.2
通讯作者：
Dantas, Gautam
中科院分区：
文献类型：
--
作者：
Sommer, Morten O. A.;Church, George M.;Dantas, Gautam
人类致病菌中越来越多的耐多药水平正在损害我们治疗传染病的能力。由于抗生素耐药性决定因素很容易通过横向基因转移在细菌之间交换，因此研究病原体可获得的抗生素耐药性储存库的兴趣越来越大。由于在疾病进展过程中与病原体接触和遗传交换的可能性很高，人类微生物群可能是最容易获得的耐药基因储存库，因此值得特别注意。事实上，许多先前的研究已经证明了从人类微生物群培养的分离株中存在大量的抗生素耐药性。通过应用宏基因组功能选择，我们最近证明了人类微生物组中耐药基因的功能库比以前使用依赖培养的方法所建议的要多样化得多。我们发现从人类粪便样本中培养的变形杆菌中获得的许多抗性基因与人类病原体所携带的抗性基因相同，这为这种抗性机制的近期遗传交换提供了强有力的支持。相比之下，与公共数据库中的所有已知基因相比，我们从相同样本中通过培养独立宏基因组取样鉴定出的大多数抗性基因都是新的。虽然这清楚地表明，难以培养的大部分人类微生物组的抗生素抗性库严重不足，但它也可能表明，在这些细菌和容易培养的人类病原体之间存在横向基因转移障碍。如果我们希望扭转多药耐药感染的趋势，我们必须紧急致力于定量表征由我们不同的人类微生物组编码的耐药库，特别关注这些库与其他微生物群落的交换途径。
The increasing levels of multi-drug resistance in human pathogenic bacteria are compromising our ability to treat infectious disease. Since antibiotic resistance determinants are readily exchanged between bacteria through lateral gene transfer, there is an increasing interest in investigating reservoirs of antibiotic resistance accessible to pathogens. Due to the high likelihood of contact and genetic exchange with pathogens during disease progression, the human microflora warrants special attention as perhaps the most accessible reservoir of resistance genes. Indeed, numerous previous studies have demonstrated substantial antibiotic resistance in cultured isolates from the human microflora. By applying metagenomic functional selections, we recently demonstrated that the functional repertoire of resistance genes in the human microbiome is much more diverse than suggested using previous culture-dependent methods. We showed that many resistance genes from cultured proteobacteria from human fecal samples are identical to resistance genes harbored by human pathogens, providing strong support for recent genetic exchange of this resistance machinery. In contrast, most of the resistance genes we identified with culture independent metagenomic sampling from the same samples were novel when compared to all known genes in public databases. While this clearly demonstrates that the antibiotic resistance reservoir of the large fraction of the human microbiome recalcitrant to culturing is severely under sampled, it may also suggest that barriers exist to lateral gene transfer between these bacteria and readily cultured human pathogens. If we hope to turn the tide against multidrug resistant infections, we must urgently commit to quantitatively characterizing the resistance reservoirs encoded by our diverse human microbiomes, with a particular focus on routes of exchange of these reservoirs with other microbial communities.