Clinically relevant antibiotic resistance genes are linked to a limited set of taxa within gut microbiome worldwide.
Clinically relevant antibiotic resistance genes are linked to a limited set of taxa within gut microbiome worldwide.
复制标题
DOI：
10.1038/s41467-023-42998-6
复制
发表时间：
2023-11-14
影响因子：
16.6
通讯作者：
Brito, Ilana L.
中科院分区：
文献类型：
--
作者：
Diebold, Peter J.;Rhee, Matthew W.;Shi, Qiaojuan;Trung, Nguyen Vinh;Umrani, Fayaz;Ahmed, Sheraz;Kulkarni, Vandana;Deshpande, Prasad;Alexander, Mallika;Thi Hoa, Ngo;Christakis, Nicholas A.;Iqbal, Najeeha Talat;Ali, Syed Asad;Mathad, Jyoti S.;Brito, Ilana L.
抗菌素耐药(AR)基因的获得使重要病原菌对抗生素几乎或完全没有反应。有人认为，病原体从肠道微生物区系获得AR特征，这些微生物区系共同充当全球AR基因的储存库，这些基因赋予所有类别的抗生素以抗药性。然而，只有AR基因的一个子集对临床相关的抗生素产生耐药性，尽管这些AR基因图谱很好地描述了常见病原体的特征，但对它们的分类关联和在肠道微生物区系的不同成员中的转移潜力知之甚少。我们研究了来自33个国家的14,850个人类元基因组和1666个环境元基因组，以及近600,000个分离的基因组，以深入了解临床相关AR基因的全球流行情况和分类范围。我们发现，一些最受关注的AR基因，如编码头孢菌素酶CTX-M和碳青霉烯酶KPC、IMP、NDM和VIM的基因，在分类上仍然局限于变形杆菌。即使是人类肠道微生物组中最常见的碳青霉烯酶基因CFIA，尽管是在可动员的质粒上发现的，但仍然严格限制在类杆菌上。我们在来自印度、洪都拉斯、巴基斯坦和越南的肠道微生物组样本中，使用高灵敏度的单细胞融合聚合酶链式反应方法证实了这些发现。聚焦于一组编码碳青霉烯酶和头孢菌素酶的基因，到目前为止，这些基因仅限于类杆菌属物种，我们发现在不同的门中有效所需的突变很少，这引发了为什么这些基因没有更广泛地传播的问题。总体而言，这些数据表明，全球流行的、临床相关的AR基因尚未在不同的共生肠道微生物区系中确立自己的地位。共生肠道细菌中的抗菌素耐药基因(ARGs)可能是病原菌获取的储存库。在这里，作者评估了args在肠道微生物群中的分布和转移潜力，并发现临床上重要的args在分类学上是受限的，尽管它与可移动的质粒有关。
The acquisition of antimicrobial resistance (AR) genes has rendered important pathogens nearly or fully unresponsive to antibiotics. It has been suggested that pathogens acquire AR traits from the gut microbiota, which collectively serve as a global reservoir for AR genes conferring resistance to all classes of antibiotics. However, only a subset of AR genes confers resistance to clinically relevant antibiotics, and, although these AR gene profiles are well-characterized for common pathogens, less is known about their taxonomic associations and transfer potential within diverse members of the gut microbiota. We examined a collection of 14,850 human metagenomes and 1666 environmental metagenomes from 33 countries, in addition to nearly 600,000 isolate genomes, to gain insight into the global prevalence and taxonomic range of clinically relevant AR genes. We find that several of the most concerning AR genes, such as those encoding the cephalosporinase CTX-M and carbapenemases KPC, IMP, NDM, and VIM, remain taxonomically restricted to Proteobacteria. Even cfiA, the most common carbapenemase gene within the human gut microbiome, remains tightly restricted to Bacteroides, despite being found on a mobilizable plasmid. We confirmed these findings in gut microbiome samples from India, Honduras, Pakistan, and Vietnam, using a high-sensitivity single-cell fusion PCR approach. Focusing on a set of genes encoding carbapenemases and cephalosporinases, thus far restricted to Bacteroides species, we find that few mutations are required for efficacy in a different phylum, raising the question of why these genes have not spread more widely. Overall, these data suggest that globally prevalent, clinically relevant AR genes have not yet established themselves across diverse commensal gut microbiota. Antimicrobial resistance genes (ARGs) in commensal gut bacteria may act as a reservoir for acquisition by pathogens. Here, the authors assess the distribution and transfer potential of ARGs in gut microbiomes and find that clinically important ARGs are taxonomically restricted despite being associated with mobile plasmids
登录
查看更多内容
影响因子：
6.4
作者：
Coyne MJ;Zitomersky NL;McGuire AM;Earl AM;Comstock LE
通讯作者：
Comstock LE
影响因子：
14.9
作者：
Alcock, Brian P.;Huynh, William;Chalil, Romeo;Smith, Keaton W.;Raphenya, Amogelang R.;Wlodarski, Mateusz A.;Edalatmand, Arman;Petkau, Aaron;Syed, Sohaib A.;Tsang, Kara K.;Baker, Sheridan J. C.;Dave, Mugdha;McCarthy, Madeline C.;Mukiri, Karyn M.;Nasir, Jalees A.;Golbon, Bahar;Imtiaz, Hamna;Jiang, Xingjian;Kaur, Komal;Kwong, Megan;Liang, Zi Cheng;Niu, Keyu C.;Shan, Prabakar;Yang, Jasmine Y. J.;Gray, Kristen L.;Hoad, Gemma R.;Jia, Baofeng;Bhando, Timsy;Carfrae, Lindsey A.;Farha, Maya A.;French, Shawn;Gordzevich, Rodion;Rachwalski, Kenneth;Tu, Megan M.;Bordeleau, Emily;Dooley, Damion;Griffiths, Emma;Zubyk, Haley L.;Brown, Eric D.;Maguire, Finlay;Beiko, Robert G.;Hsiao, William W. L.;Brinkman, Fiona S. L.;Van Domselaar, Gary;McArthur, Andrew G.
通讯作者：
McArthur, Andrew G.
影响因子：
28.3
作者：
Gibson, Molly K.;Wang, Bin;Ahmadi, Sara;Burnham, Carey-Ann D.;Tarr, Phillip I.;Warner, Barbara B.;Dantas, Gautam
通讯作者：
Dantas, Gautam
影响因子：
3.7
作者：
通讯作者：
--
影响因子：
3.7
作者：
Vien le TM;Minh NN;Thuong TC;Khuong HD;Nga TV;Thompson C;Campbell JI;de Jong M;Farrar JJ;Schultsz C;van Doorn HR;Baker S
通讯作者：
Baker S