Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
1] Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA [2] Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA [3] Department of Biomedical Engineering, Washington University, St Louis, MO, USA.
ISME J. 2015 Jan;9(1):207-16. doi: 10.1038/ismej.2014.106. Epub 2014 Jul 8.
Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.
抗生素耐药性是一个严重的临床问题，具有重要的生态层面。虽然人类病原体中的抗生素耐药性仍以惊人的速度上升，但环境耐药性对人类健康的影响尚不清楚。为了研究人类相关和环境耐药组之间的关系，我们分析了从土壤和人类肠道微生物群中针对 18 种临床相关抗生素的功能宏基因组选择，以及一组多药耐药培养的土壤分离物。这些分析得益于 Resfams，这是一个新的经过精心整理的蛋白质家族数据库，以及相关的高度精确和准确的轮廓隐马尔可夫模型，这些模型经过抗生素耐药性功能的验证，并按本体论组织。我们证明，导致在环境和人类相关微生物群落中观察到的耐药谱的抗生素耐药性功能在生态之间存在显著差异。在生态之间差异最大的抗生素耐药性功能提供了对β-内酰胺类和四环素类的耐药性，这两类抗生素是临床和农业中使用最广泛的抗生素之一。我们还分析了 6000 多个测序微生物基因组的抗生素耐药基因组成，发现生态和系统发育都显著富集了耐药功能。总之，我们的结果表明，环境和人类相关的微生物群落含有不同的耐药基因，这表明抗生素耐药性功能在很大程度上受到生态的限制。
