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

Collie D, Glendinning L, Govan J, Wright S, Thornton E, Tennant P, Doherty C, McLachlan G - PLoS ONE (2015)

Bottom Line: With only one exception the reduction was seen in both direct and remote lung segments.This reduction, coupled with generally increasing or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment.The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT

Background: 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).

Methodology/principal findings: 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 or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment.

Conclusions/significance: The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection.

No MeSH data available.


Related in: MedlinePlus

Change in Gram negative bacteria (excluding Pseudomonadales) in Pre- and Post-samples.Line charts indicating the percentage of Gram negative bacteria in PSB samples derived prior to (Pre) and 14 days after infection with P.aer (Post) from sheep treated with daily intravenous injections of A. saline (Placebo), or B. CMS (CMS) between days 7–14. Symbols reflect the identity of sheep according to the legend entries, with filled symbols reflecting samples derived from directly infected lung segments (LC), partially filled symbols from remote segment RA, and open symbols from remote segment RVD1.
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pone.0142097.g007: Change in Gram negative bacteria (excluding Pseudomonadales) in Pre- and Post-samples.Line charts indicating the percentage of Gram negative bacteria in PSB samples derived prior to (Pre) and 14 days after infection with P.aer (Post) from sheep treated with daily intravenous injections of A. saline (Placebo), or B. CMS (CMS) between days 7–14. Symbols reflect the identity of sheep according to the legend entries, with filled symbols reflecting samples derived from directly infected lung segments (LC), partially filled symbols from remote segment RA, and open symbols from remote segment RVD1.

Mentions: We determined whether systemic therapy with CMS had any influence on the proportion of Gram negative bacteria (excluding Pseudomonadales) in lung microbiota. Whereas the presence of local lung infection with Ps aer did not significantly alter the proportion of Gram negative bacteria (excluding Pseudomonadales)(Fig 7A) in the lung segments of sheep treated with placebo (Paired t-test on Pre-Post differences (n = 4), P = 0.741), all of the direct segments and all except one of the remote segments (7/8) of sheep treated with CMS experienced a reduction in the proportion of Gram negative bacteria (excluding Pseudomonadales)(Fig 7B). The reduction in the proportion of G-ve bacteria (excluding Pseudomonadales) in lung segments of the CMS group was significant (Paired t-test on Pre-Post differences (n = 4), P = 0.040). When only the remote lung segments were included in this analysis, again the proportion of Gram negative bacteria (excluding Pseudomonadales) showed no significant change in response to infection in the placebo group whereas there was a significant reduction in this proportion in the sheep treated with CMS (Paired t-test on Pre-Post differences (n = 4), P = 0.979, and P = 0.044 respectively).


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

Collie D, Glendinning L, Govan J, Wright S, Thornton E, Tennant P, Doherty C, McLachlan G - PLoS ONE (2015)

Change in Gram negative bacteria (excluding Pseudomonadales) in Pre- and Post-samples.Line charts indicating the percentage of Gram negative bacteria in PSB samples derived prior to (Pre) and 14 days after infection with P.aer (Post) from sheep treated with daily intravenous injections of A. saline (Placebo), or B. CMS (CMS) between days 7–14. Symbols reflect the identity of sheep according to the legend entries, with filled symbols reflecting samples derived from directly infected lung segments (LC), partially filled symbols from remote segment RA, and open symbols from remote segment RVD1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4636361&req=5

pone.0142097.g007: Change in Gram negative bacteria (excluding Pseudomonadales) in Pre- and Post-samples.Line charts indicating the percentage of Gram negative bacteria in PSB samples derived prior to (Pre) and 14 days after infection with P.aer (Post) from sheep treated with daily intravenous injections of A. saline (Placebo), or B. CMS (CMS) between days 7–14. Symbols reflect the identity of sheep according to the legend entries, with filled symbols reflecting samples derived from directly infected lung segments (LC), partially filled symbols from remote segment RA, and open symbols from remote segment RVD1.
Mentions: We determined whether systemic therapy with CMS had any influence on the proportion of Gram negative bacteria (excluding Pseudomonadales) in lung microbiota. Whereas the presence of local lung infection with Ps aer did not significantly alter the proportion of Gram negative bacteria (excluding Pseudomonadales)(Fig 7A) in the lung segments of sheep treated with placebo (Paired t-test on Pre-Post differences (n = 4), P = 0.741), all of the direct segments and all except one of the remote segments (7/8) of sheep treated with CMS experienced a reduction in the proportion of Gram negative bacteria (excluding Pseudomonadales)(Fig 7B). The reduction in the proportion of G-ve bacteria (excluding Pseudomonadales) in lung segments of the CMS group was significant (Paired t-test on Pre-Post differences (n = 4), P = 0.040). When only the remote lung segments were included in this analysis, again the proportion of Gram negative bacteria (excluding Pseudomonadales) showed no significant change in response to infection in the placebo group whereas there was a significant reduction in this proportion in the sheep treated with CMS (Paired t-test on Pre-Post differences (n = 4), P = 0.979, and P = 0.044 respectively).

Bottom Line: With only one exception the reduction was seen in both direct and remote lung segments.This reduction, coupled with generally increasing or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment.The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT

Background: 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).

Methodology/principal findings: 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 or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment.

Conclusions/significance: The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection.

No MeSH data available.


Related in: MedlinePlus