Spatial distribution of microbial communities in the cystic fibrosis lung

Department of Biology, San Diego State University, San Diego, CA, USA.
The ISME Journal (Impact Factor: 9.3). 07/2011; 6(2):471-4. DOI: 10.1038/ismej.2011.104
Source: PubMed

ABSTRACT Cystic fibrosis (CF) is a common fatal genetic disorder with mortality most often resulting from microbial infections of the lungs. Culture-independent studies of CF-associated microbial communities have indicated that microbial diversity in the CF airways is much higher than suggested by culturing alone. However, these studies have relied on indirect methods to sample the CF lung such as expectorated sputum and bronchoalveolar lavage (BAL). Here, we characterize the diversity of microbial communities in tissue sections from anatomically distinct regions of the CF lung using barcoded 16S amplicon pyrosequencing. Microbial communities differed significantly between different areas of the lungs, and few taxa were common to microbial communities in all anatomical regions surveyed. Our results indicate that CF lung infections are not only polymicrobial, but also spatially heterogeneous suggesting that treatment regimes tailored to dominant populations in sputum or BAL samples may be ineffective against infections in some areas of the lung.

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Available from: Dana Willner, Sep 27, 2015
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    • "Indeed, reads of P. aeruginosa were obtained in all but one P. aeruginosa positive-sample from which P. aeruginosa was only detected using qPCR. The 13 predominant genera identified in the present study are commonly found in CF respiratory tract microbiota (Willner et al. 2012; Venkataraman et al. 2015; Tunney et al. 2008; Carmody et al. 2013). Nine of them have been described to be the most abundant genera in healthy lungs (Wat et al. 2008). "
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    ABSTRACT: Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning‑sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter‑ and intra‑individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state.
    SpringerPlus 08/2015; 4(1). DOI:10.1186/s40064-015-1207-0
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    • "However, fermentative signals observed from CF samples were not likely from saliva contamination, because the characteristic gas bubble formation was only present during exacerbation and never at times of stability even though sampling procedures were identical. Oral bacteria have been detected before in the upper airways and sputum of CF patients (Tunney et al., 2008; Worlitzsch et al., 2009; Goddard et al., 2012; Willner et al., 2012), and our results indicate that they colonize lung mucus and may contribute significantly to exacerbations. However, it cannot be known whether these bacteria drive exacerbation onset or whether their growth is favored during the conditions of an exacerbating CF lung. "
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    ABSTRACT: There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.
    The ISME Journal 12/2014; 9(4). DOI:10.1038/ismej.2014.234 · 9.30 Impact Factor
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    • "As a result, phage therapy could prove especially effective against chronic bacterial infections that cannot anymore be eradicated with antibiotics. Even though potential complications might rise from the spatial distribution and within- and between-species diversity of bacterial infections [57]–[59], identifying similar fitness trade-offs for bacterial survival between natural and clinical environments could serve as a starting point for developing potential alternatives for antibiotics. For example, within-host specialization could make bacteria more susceptible to bacterium-specific toxins (bacteriocins) that are used in intraspecific bacterial competition in natural environments [47], [60], but might not be needed in the lungs of CF patients. "
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    ABSTRACT: Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations.
    PLoS ONE 09/2013; 8(9):e75380. DOI:10.1371/journal.pone.0075380 · 3.23 Impact Factor
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