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Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X)
The emergence of tet(X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet(X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693923/ https://www.ncbi.nlm.nih.gov/pubmed/34935428 http://dx.doi.org/10.1128/Spectrum.01164-21 |
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author | Zhang, Rong-min Sun, Jian Sun, Ruan-yang Wang, Min-ge Cui, Chao-yue Fang, Liang-xing Liao, Mei-na Lu, Xiao-qing Liu, Yong-xin Liao, Xiao-Ping Liu, Ya-Hong |
author_facet | Zhang, Rong-min Sun, Jian Sun, Ruan-yang Wang, Min-ge Cui, Chao-yue Fang, Liang-xing Liao, Mei-na Lu, Xiao-qing Liu, Yong-xin Liao, Xiao-Ping Liu, Ya-Hong |
author_sort | Zhang, Rong-min |
collection | PubMed |
description | The emergence of tet(X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet(X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from worldwide. These tet(X) genes were dominated by tet(X2)-like orthologs but we also identified 12 samples carrying novel tet(X) genes, designed tet(X45), tet(X46), and tet(X47), were resistant to tigecycline. The metagenomic analysis indicated these tet(X) genes distributed in anaerobes dominated by Bacteroidaceae (78.89%) of human-gut origin. Two mobile elements ISBf11 and IS4351 were most likely to promote the transmission of these tet(X2)-like orthologs between Bacteroidaceae and Riemerella anatipestifer. tet(X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant genes tet(X45), tet(X46), and tet(X47). Further tracing these tet(X) in single bacterial isolate from public repository indicated tet(X) genes were present as early as 1960s in R. anatipestifer that was the primary tet(X) carrier at early stage (before 2000). The tet(X2) and non-tet(X2) orthologs were primarily distributed in humans and food animals respectively, and non-tet(X2) were dominated by tet(X3) and tet(X4). Genomic comparison indicated these tet(X) genes were likely to be generated during tet(X) transmission between Flavobacteriaceae and E. coli/Acinetobacter spp., and ISCR2 played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of tet(X). In addition, Bacteroidaceae of human-gut origin was an important hidden reservoir and mutational incubator for the mobile tet(X) genes that enabled spread to facultative anaerobes and aerobes. IMPORTANCE The emergence of the tigecycline resistance gene tet(X) has posed a severe threat to public health. However, reports of its origin and distribution in human remain rare. Here, we explore the origin and distribution of tet(X) from large-scale metagenomic data of human-gut origin and public repository. This study revealed the emergency of tet(X) gene in 1960s, which has refreshed a previous standpoint that the earliest presence of tet(X) was in 1980s. The metagenomic analysis from data mining covered the unculturable bacteria, which has overcome the traditional bacteria isolating and purificating technologies, and the analysis indicated that the Bacteroidaceae of human-gut origin was an important hidden reservoir for tet(X) that enabled spread to facultative anaerobes and aerobes. The continuous monitoring of mobile tigecycline resistance determinants from both culturable and unculturable microorganisms is imperative for understanding and tackling the dissemination of tet(X) genes in both the health care and agricultural sectors. |
format | Online Article Text |
id | pubmed-8693923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-86939232021-12-27 Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) Zhang, Rong-min Sun, Jian Sun, Ruan-yang Wang, Min-ge Cui, Chao-yue Fang, Liang-xing Liao, Mei-na Lu, Xiao-qing Liu, Yong-xin Liao, Xiao-Ping Liu, Ya-Hong Microbiol Spectr Research Article The emergence of tet(X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet(X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from worldwide. These tet(X) genes were dominated by tet(X2)-like orthologs but we also identified 12 samples carrying novel tet(X) genes, designed tet(X45), tet(X46), and tet(X47), were resistant to tigecycline. The metagenomic analysis indicated these tet(X) genes distributed in anaerobes dominated by Bacteroidaceae (78.89%) of human-gut origin. Two mobile elements ISBf11 and IS4351 were most likely to promote the transmission of these tet(X2)-like orthologs between Bacteroidaceae and Riemerella anatipestifer. tet(X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant genes tet(X45), tet(X46), and tet(X47). Further tracing these tet(X) in single bacterial isolate from public repository indicated tet(X) genes were present as early as 1960s in R. anatipestifer that was the primary tet(X) carrier at early stage (before 2000). The tet(X2) and non-tet(X2) orthologs were primarily distributed in humans and food animals respectively, and non-tet(X2) were dominated by tet(X3) and tet(X4). Genomic comparison indicated these tet(X) genes were likely to be generated during tet(X) transmission between Flavobacteriaceae and E. coli/Acinetobacter spp., and ISCR2 played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of tet(X). In addition, Bacteroidaceae of human-gut origin was an important hidden reservoir and mutational incubator for the mobile tet(X) genes that enabled spread to facultative anaerobes and aerobes. IMPORTANCE The emergence of the tigecycline resistance gene tet(X) has posed a severe threat to public health. However, reports of its origin and distribution in human remain rare. Here, we explore the origin and distribution of tet(X) from large-scale metagenomic data of human-gut origin and public repository. This study revealed the emergency of tet(X) gene in 1960s, which has refreshed a previous standpoint that the earliest presence of tet(X) was in 1980s. The metagenomic analysis from data mining covered the unculturable bacteria, which has overcome the traditional bacteria isolating and purificating technologies, and the analysis indicated that the Bacteroidaceae of human-gut origin was an important hidden reservoir for tet(X) that enabled spread to facultative anaerobes and aerobes. The continuous monitoring of mobile tigecycline resistance determinants from both culturable and unculturable microorganisms is imperative for understanding and tackling the dissemination of tet(X) genes in both the health care and agricultural sectors. American Society for Microbiology 2021-12-22 /pmc/articles/PMC8693923/ /pubmed/34935428 http://dx.doi.org/10.1128/Spectrum.01164-21 Text en Copyright © 2021 Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhang, Rong-min Sun, Jian Sun, Ruan-yang Wang, Min-ge Cui, Chao-yue Fang, Liang-xing Liao, Mei-na Lu, Xiao-qing Liu, Yong-xin Liao, Xiao-Ping Liu, Ya-Hong Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) |
title | Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) |
title_full | Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) |
title_fullStr | Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) |
title_full_unstemmed | Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) |
title_short | Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X) |
title_sort | source tracking and global distribution of the tigecycline non-susceptible tet(x) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693923/ https://www.ncbi.nlm.nih.gov/pubmed/34935428 http://dx.doi.org/10.1128/Spectrum.01164-21 |
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