摘要
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土壤被认为是抗生素抗性基因（ARGs）的主要宿主，蕴藏着地球上最多样的自然进化的ARGs。多药耐药基因是ARGs的一类，其在自然土壤生态系统中的高流行率最近引起了人们的关注。由于这些基因中的大多数表达质子动力（PMF）驱动的外排泵，研究土壤pH是否是选择多药外排泵基因的决定因素，从而形成土壤抗性是非常有意义的。在这项研究中，我们从多个生态系统中收集了108种pH值在4.37至9.69之间的土壤，并分析了宏基因组和宏基因组组装基因组的ARGs组成。我们观察到多药外排泵基因在酸性土壤抗性组中富集，其丰度具有显著的土壤pH依赖性。这反映了高土壤质子活性对多药外排泵基因的益处，尤其是对PMF驱动的内膜转移酶。此外，我们通过应用逐步回归和随机森林模型拟合等生态分析工具，初步表明了pH值塑造土壤抗性的假定微生物参与者。质子活性对形成抗性的决定性影响比任何其他研究因素都更有影响力，因此，我们重新审视了土壤因素对土壤抗性的影响；即土壤因素对抗性机制的确定性选择可能导致ARG组成的自下而上的形成。本文建议在评估人类驱动的ARG传播时考虑耐药性的这种自然发展机制。
Abstract
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Soil is recognized as the major reservoir of antibiotic resistance genes (ARGs), harboring the most diverse naturally evolved ARGs on the planet. Multidrug resistance genes are a class of ARGs, and their high prevalence in natural soil ecosystems has recently raised concerns. Since most of these genes express proton motive force (PMF) driven efflux pumps, studying whether soil pH is a determinant for the selection of multidrug efflux pump genes and thus shaping the soil resistome are of great interest. In this study, we collected 108 soils with pH values ranging from 4.37 to 9.69 from multiple ecosystems and profiled the composition of ARGs for metagenomes and metagenome-assembled genomes. We observed the multidrug efflux pump genes enriched in the acidic soil resistome, and their abundances have significant soil pH dependence. This reflects the benefits of high soil proton activity on the multidrug efflux pump genes, especially for the PMF-driven inner membrane transferase. In addition, we preliminary indicate the putative microbial participants in pH shaping the soil resistome by applying ecological analyzing tools such as stepwise regression and random forest model fitting. The decisive influence of proton activity on shaping the resistome is more impactful than any other examined factors, and as the consequence, we revisited the influence of edaphic factors on the soil resistome; i.e., the deterministic selection of resistance mechanisms by edaphic factors could lead to the bottom-up shaping of the ARG composition. Such natural developing mechanisms of the resistome are herein suggested to be considered in assessing human-driven ARG transmissions.

https://pubs.acs.org/doi/abs/10.1021/acs.est.2c06684