title: Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention.
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.
authors.affiliation: NERC Centre for Ecology & Hydrology, Wallingford, UK.|Institute of Pharmaceutical Science, Molecular Microbiology Research Laboratory, King's College London, London SE1 9NH, UK.
authors.forename: Leah
authors.initials: L
authors.lastname: Cuthbertson
authors.affiliation: SAHMRI Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Geraint B
authors.initials: GB
authors.lastname: Rogers
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.|Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Walker
authors.affiliation: NERC Centre for Ecology & Hydrology, Wallingford, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Oliver
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Green
authors.affiliation: Cystic Fibrosis Unit, Southampton University Hospitals NHS Trust, Southampton, UK.
authors.forename: Thomas W V
authors.initials: TW
authors.lastname: Daniels
authors.affiliation: Cystic Fibrosis Unit, Southampton University Hospitals NHS Trust, Southampton, UK.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Carroll
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Institute of Pharmaceutical Science, Molecular Microbiology Research Laboratory, King's College London, London SE1 9NH, UK.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bruce
authors.affiliation: NERC Centre for Ecology & Hydrology, Wallingford, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: van der Gast
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy / Q000382:microbiology* / Q000503:physiopathology*; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012141:Respiratory Tract Infections / Q000150:complications / Q000382:microbiology*; D013183:Sputum / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S