Department of Genetics, Harvard Medical School, Boston, MA, USA.
Virulence. 2010 Jul-Aug;1(4):299-303. doi: 10.4161/viru.1.4.12010.
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.
人类病原菌的耐药水平不断上升，正在削弱我们治疗感染性疾病的能力。由于抗生素耐药决定因素可通过水平基因转移在细菌之间轻易交换，因此人们越来越关注可被病原菌利用的抗生素耐药库。由于在疾病进展过程中与病原菌接触和基因交换的可能性很高，人类微生物群值得特别关注，因为它可能是最容易获得耐药基因的库。事实上，许多先前的研究已经证明了从人类微生物群中培养的分离物中存在大量抗生素耐药性。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谱比以前使用的基于培养的方法所显示的要多样化得多。我们发现，从人类粪便样本中培养的变形菌的许多耐药基因与人类病原体所携带的耐药基因相同，这为该耐药机制的近期基因交换提供了有力支持。相比之下，与从相同样本中独立培养的宏基因组采样相比，我们用这种方法识别的大多数耐药基因与所有已知的公共数据库中的基因都不同。虽然这清楚地表明，大量对培养具有抗性的人类微生物组的抗生素耐药库严重未被采样，但这也可能表明，这些细菌与易于培养的人类病原体之间存在水平基因转移的障碍。如果我们希望扭转对抗生素耐药性感染的趋势，就必须紧急致力于定量描述我们多样化的人类微生物组所编码的耐药库，特别要关注这些库与其他微生物群落之间的交换途径。
