Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium

Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeru...

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Bibliographic Details
Published in:PloS one 2015-11, Vol.10 (11), p.e0142097-e0142097
Main Authors: Collie, David, Glendinning, Laura, Govan, John, Wright, Steven, Thornton, Elisabeth, Tennant, Peter, Doherty, Catherine, McLachlan, Gerry
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - administration & dosage
Antibiotics
Bacteria
Bacterial Load
Bronchoalveolar Lavage Fluid - microbiology
Care and treatment
Chronic Disease
Chronic infection
Chronic obstructive pulmonary disease
Colistin - administration & dosage
Colistin - analogs & derivatives
Community composition
Complications and side effects
Cystic fibrosis
Development and progression
Disease Models, Animal
Dosage and administration
Drug therapy
Female
Gene expression
Gram-negative bacteria
Infections
Injections, Intravenous
Intravenous administration
Lung - microbiology
Lung - pathology
Lung diseases
Lungs
Male
Microbiota
Microorganisms
Morbidity
Pathogenesis
Pathogens
Patient outcomes
Pseudomonas aeruginosa
Pseudomonas aeruginosa - genetics
Pseudomonas aeruginosa - isolation & purification
Pseudomonas Infections - drug therapy
Pseudomonas Infections - microbiology
Pseudomonas Infections - pathology
Reduction
Respiratory function
Respiratory Tract Infections - drug therapy
Respiratory Tract Infections - microbiology
Respiratory Tract Infections - pathology
Ribosomal DNA
Segments
Sheep
Sheep, Domestic
Sodium
Sputum
Studies
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Summary:Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS). We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota communities after infection. Whilst treatment with CMS appeared to have little impact on microbial community composition after infection, or the change undergone by communities in reaching that state, when Gram negative organisms (excluding Pseudomonadales) were considered together as a group there was a significant decrease in their relative proportion that was only observed in the sheep treated with CMS. With only one exception the reduction was seen in both direct and remote lung segments. This reduction, coupled with generally increasing
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0142097