Department of Genetic Medicine and Development, University of Geneva Medical School and Swiss Institute of Bioinformatics, Geneva, Switzerland.
Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russian Federation.
Environ Microbiol. 2018 Jun;20(6):2288-2300. doi: 10.1111/1462-2920.14276. Epub 2018 Aug 7.
Antibiotic resistance is increasing among pathogens, and the human microbiome contains a reservoir of antibiotic resistance genes. Acidaminococcus intestini is the first Negativicute bacterium (Gram-negative Firmicute) shown to be resistant to beta-lactam antibiotics. Resistance is conferred by the aci1 gene, but its evolutionary history and prevalence remain obscure. We discovered that ACI-1 proteins are phylogenetically distinct from beta-lactamases of Gram-positive Firmicutes and that aci1 occurs in bacteria scattered across the Negativicute clade, suggesting lateral gene transfer. In the reference A. intestini RyC-MR95 genome, we found transposons residing within a tailed prophage context are likely vehicles for aci1's mobility. We found aci1 in 56 (4.4%) of 1,267 human gut metagenomes, mostly hosted within A. intestini, and, where could be determined, mostly within a consistent mobile element constellation. These samples are from Europe, China and the USA, showing that aci1 is distributed globally. We found that for most Negativicute assemblies with aci1, the prophage observed in A. instestini is absent, but in all cases aci1 is flanked by varying transposons. The chimeric mobile elements we identify here likely have a complex evolutionary history and potentially provide multiple complementary mechanisms for antibiotic resistance gene transfer both within and between cells.
抗生素耐药性在病原体中不断增加，而人类微生物组中含有大量抗生素耐药基因。肠杆菌属是第一个被证明对β-内酰胺类抗生素具有耐药性的阴性杆菌（革兰氏阴性Firmicutes）。耐药性由aci1 基因赋予，但它的进化历史和流行情况仍不清楚。我们发现 ACI-1 蛋白在系统发育上与革兰氏阳性Firmicutes 的β-内酰胺酶不同，并且 aci1 存在于 Negativicutes 进化枝中分散的细菌中，表明存在横向基因转移。在参考 A. intestini RyC-MR95 基因组中，我们发现位于尾部噬菌体背景下的转座子可能是 aci1 可移动性的载体。我们在 1267 个人类肠道宏基因组中的 56 个（4.4%）中发现了 aci1，主要存在于肠杆菌属内，并且在可以确定的情况下，主要存在于一致的移动元件组合内。这些样本来自欧洲、中国和美国，表明 aci1 分布在全球范围内。我们发现，对于大多数带有 aci1 的 Negativicute 组装体，在 A. instestini 中观察到的噬菌体是不存在的，但在所有情况下，aci1 都被不同的转座子包围。我们在这里鉴定的嵌合移动元件可能具有复杂的进化历史，并且可能为抗生素耐药基因在细胞内和细胞间的转移提供多种互补机制。
