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Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention
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Cuthbertson, Leah, Rogers, Geraint B., Walker, Alan W., Oliver, Anna, Green, Laura E., Daniels, Thomas W. V., Carroll, Mary P., Parkhill, Julian, Bruce, Kenneth D. and van der Gast, Christopher J. (2016) Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. The ISME Journal, 10 (5). pp. 1081-1091. doi:10.1038/ismej.2015.198
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Official URL: http://dx.doi.org/10.1038/ismej.2015.198
Abstract
Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||
| Library of Congress Subject Headings (LCSH): | Cystic fibrosis -- Treatment | ||||||||||
| Journal or Publication Title: | The ISME Journal | ||||||||||
| Publisher: | Nature Publishing Group | ||||||||||
| ISSN: | 1751-7362 | ||||||||||
| Official Date: | May 2016 | ||||||||||
| Dates: |
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| Date of first compliant deposit: | 14 July 2016 | ||||||||||
| Volume: | 10 | ||||||||||
| Number: | 5 | ||||||||||
| Page Range: | pp. 1081-1091 | ||||||||||
| DOI: | 10.1038/ismej.2015.198 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||
| Funder: | Natural Environment Research Council (Great Britain) (NERC), Wellcome Trust (London, England), Anna Trust, Scotland. Rural and Environment Science and Analytical Services (RESAS) | ||||||||||
| Grant number: | NE/H019456/1 (NERC), 098051 (WT), KB2008 (AT) |
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