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短双歧杆菌中与 rRNA 甲基化酶基因同源的基因赋予红霉素和克林霉素耐药性。

A Gene Homologous to rRNA Methylase Genes Confers Erythromycin and Clindamycin Resistance in Bifidobacterium breve.

机构信息

Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Villaviciosa, Asturias, Spain.

Biosearch S.A., Granada, Spain.

出版信息

Appl Environ Microbiol. 2018 May 1;84(10). doi: 10.1128/AEM.02888-17. Print 2018 May 15.

Abstract

Bifidobacteria are mutualistic intestinal bacteria, and their presence in the human gut has been associated with health-promoting activities. The presence of antibiotic resistance genes in this genus is controversial, since, although bifidobacteria are nonpathogenic microorganisms, they could serve as reservoirs of resistance determinants for intestinal pathogens. However, until now, few antibiotic resistance determinants have been functionally characterized in this genus. In this work, we show that CECT7263 displays atypical resistance to erythromycin and clindamycin. In order to delimit the genomic region responsible for the observed resistance phenotype, a library of genomic DNA was constructed and a fragment of 5.8 kb containing a gene homologous to rRNA methylase genes was able to confer erythromycin resistance in This genomic region seems to be very uncommon, and homologs of the gene have been detected in only one strain of and two other strains of In this context, analysis of shotgun metagenomics data sets revealed that the gene is also uncommon in the microbiomes of adults and infants. The structural gene and its upstream region were cloned into a -sensitive strain, which became resistant after acquiring the genetic material. conjugation experiments did not allow us to detect gene transfer to other recipients. Nevertheless, prediction of genes potentially acquired through horizontal gene transfer events revealed that the gene is located in a putative genomic island. is a very common human intestinal bacterium. Often described as a pioneer microorganism in the establishment of early-life intestinal microbiota, its presence has been associated with several beneficial effects for the host, including immune stimulation and protection against infections. Therefore, some strains of this species are considered probiotics. In relation to this, because probiotic bacteria are used for human and animal consumption, one of the safety concerns over these bacteria is the presence of antibiotic resistance genes, since the human gut is a densely populated habitat that could favor the transfer of genetic material to potential pathogens. In this study, we analyzed the genetic basis responsible for the erythromycin and clindamycin resistance phenotype of CECT7263. We were able to identify and characterize a novel gene homologous to rRNA methylase genes which confers erythromycin and clindamycin resistance. This gene seems to be very uncommon in other bifidobacteria and in the gut microbiomes of both adults and infants. Even though conjugation experiments showed the absence of transferability under conditions, it has been predicted to be located in a putative genomic island recently acquired by specific bifidobacterial strains.

摘要

双歧杆菌是一种共生肠道细菌,其存在与人的肠道健康有关。该属中存在抗生素耐药基因存在争议,因为双歧杆菌虽然是非致病性微生物,但它们可能是肠道病原体耐药决定因素的储库。然而,到目前为止,该属中只有少数抗生素耐药决定因素得到了功能表征。在这项工作中,我们表明 CECT7263 对红霉素和克林霉素表现出非典型耐药性。为了划定负责观察到的耐药表型的基因组区域,构建了基因组 DNA 文库,并且能够赋予红霉素抗性的 5.8 kb 大小的基因片段包含与 rRNA 甲基化酶基因同源的基因。该基因组区域似乎非常罕见,并且在 和另外两株 中仅检测到该基因的同源物。在这种情况下,对 shotgun 宏基因组数据集的分析表明,该基因在成人和婴儿的微生物组中也很少见。结构基因及其上游区域被克隆到 - 敏感株中,该株在获得遗传物质后变得耐药。 接合实验未能使我们检测到向其他受体的基因转移。然而,通过水平基因转移事件预测潜在获得的基因表明,该基因位于一个假定的基因组岛中。是一种非常常见的人类肠道细菌。通常被描述为早期生命肠道微生物群建立的先驱微生物,其存在与宿主的多种有益影响相关,包括免疫刺激和对感染的保护。因此,该物种的一些菌株被认为是益生菌。关于这一点,因为益生菌被用于人类和动物的食用,人们对这些细菌的安全性关注之一是存在抗生素耐药基因,因为人类肠道是一个人口密集的栖息地,可能有利于将遗传物质转移给潜在的病原体。在这项研究中,我们分析了负责 CECT7263 红霉素和克林霉素耐药表型的遗传基础。我们能够鉴定和表征一种新型基因,该基因与 rRNA 甲基化酶基因同源,赋予红霉素和克林霉素耐药性。该基因在其他双歧杆菌中似乎非常罕见,在成人和婴儿的肠道微生物组中也很少见。尽管接合实验表明在 条件下没有可转移性,但已预测其位于最近由特定双歧杆菌菌株获得的假定基因组岛中。

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