Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy
Determining the effects of antimicrobial therapies on airway microbiology at a population-level is essential. Such analysis allows, for example, surveillance of antibiotic-induced changes in pathogen prevalence, the emergence and spread of antibiotic resistance, and the transmission of multi-resista...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://purl.org/au-research/grants/nhmrc/1104000 http://hdl.handle.net/20.500.11937/80732 |
| _version_ | 1848764260641931264 |
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| author | Taylor, S.L. Leong, L.E.X. Mobegi, Fredrick Choo, J.M. Burr, L.D. Wesselingh, S. Rogers, G.B. |
| author_facet | Taylor, S.L. Leong, L.E.X. Mobegi, Fredrick Choo, J.M. Burr, L.D. Wesselingh, S. Rogers, G.B. |
| author_sort | Taylor, S.L. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Determining the effects of antimicrobial therapies on airway microbiology at a population-level is essential. Such analysis allows, for example, surveillance of antibiotic-induced changes in pathogen prevalence, the emergence and spread of antibiotic resistance, and the transmission of multi-resistant organisms. However, current analytical strategies for understanding these processes are limited. Culture- and PCR-based assays for specific microbes require the a priori selection of targets, while antibiotic sensitivity testing typically provides no insight into either the molecular basis of resistance, or the carriage of resistance determinants by the wider commensal microbiota. Shotgun metagenomic sequencing provides an alternative approach that allows the microbial composition of clinical samples to be described in detail, including the prevalence of resistance genes and virulence traits. While highly informative, the application of metagenomics to large patient cohorts can be prohibitively expensive. Using sputum samples from a randomised placebo-controlled trial of erythromycin in adults with bronchiectasis, we describe a novel, cost-effective strategy for screening patient cohorts for changes in resistance gene prevalence. By combining metagenomic screening of pooled DNA extracts with validatory quantitative PCR-based analysis of candidate markers in individual samples, we identify population-level changes in the relative abundance of specific macrolide resistance genes. This approach has the potential to provide an important adjunct to current analytical strategies, particularly within the context of antimicrobial clinical trials. |
| first_indexed | 2025-11-14T11:16:32Z |
| format | Journal Article |
| id | curtin-20.500.11937-80732 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:16:32Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-807322021-01-07T07:46:47Z Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy Taylor, S.L. Leong, L.E.X. Mobegi, Fredrick Choo, J.M. Burr, L.D. Wesselingh, S. Rogers, G.B. Antibiotic therapy DNA Metagenomic screening Determining the effects of antimicrobial therapies on airway microbiology at a population-level is essential. Such analysis allows, for example, surveillance of antibiotic-induced changes in pathogen prevalence, the emergence and spread of antibiotic resistance, and the transmission of multi-resistant organisms. However, current analytical strategies for understanding these processes are limited. Culture- and PCR-based assays for specific microbes require the a priori selection of targets, while antibiotic sensitivity testing typically provides no insight into either the molecular basis of resistance, or the carriage of resistance determinants by the wider commensal microbiota. Shotgun metagenomic sequencing provides an alternative approach that allows the microbial composition of clinical samples to be described in detail, including the prevalence of resistance genes and virulence traits. While highly informative, the application of metagenomics to large patient cohorts can be prohibitively expensive. Using sputum samples from a randomised placebo-controlled trial of erythromycin in adults with bronchiectasis, we describe a novel, cost-effective strategy for screening patient cohorts for changes in resistance gene prevalence. By combining metagenomic screening of pooled DNA extracts with validatory quantitative PCR-based analysis of candidate markers in individual samples, we identify population-level changes in the relative abundance of specific macrolide resistance genes. This approach has the potential to provide an important adjunct to current analytical strategies, particularly within the context of antimicrobial clinical trials. 2018 Journal Article http://hdl.handle.net/20.500.11937/80732 10.1186/s40248-018-0140-9 eng http://purl.org/au-research/grants/nhmrc/1104000 http://creativecommons.org/licenses/by/4.0/ fulltext |
| spellingShingle | Antibiotic therapy DNA Metagenomic screening Taylor, S.L. Leong, L.E.X. Mobegi, Fredrick Choo, J.M. Burr, L.D. Wesselingh, S. Rogers, G.B. Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy |
| title | Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy |
| title_full | Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy |
| title_fullStr | Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy |
| title_full_unstemmed | Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy |
| title_short | Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy |
| title_sort | understanding the impact of antibiotic therapies on the respiratory tract resistome: a novel pooled-template metagenomic sequencing strategy |
| topic | Antibiotic therapy DNA Metagenomic screening |
| url | http://purl.org/au-research/grants/nhmrc/1104000 http://hdl.handle.net/20.500.11937/80732 |