The polymicrobial nature of airway infections in cystic fibrosis: Cangene Gold Medal LectureThis article is based on a presentation by Dr. Christopher Sibley at the 60th Annual Meeting of the Canadian Society of Microbiologists in Hamilton, Ontario, on 15 June 2010. Dr. Sibley was the recipient of the 2010 Cangene Gold Medal as the Canadian Graduate Student Microbiologist of the Year, an annual award sponsored by Cangene Corporation intended to recognize excellence in graduate research.

2011 ◽  
Vol 57 (2) ◽  
pp. 69-77 ◽  
Author(s):  
Christopher D. Sibley ◽  
Michael G. Surette
Keyword(s):  
Cystic Fibrosis ◽  
Microbial Communities ◽  
Gold Medal ◽  
Emergent Properties ◽  
Host Interactions ◽  
Airway Infections ◽  
Future Challenges ◽  
Culture Independent ◽  
Airway Microbiome ◽  
Dynamic Communities

Microbial communities characterize the airways of cystic fibrosis (CF) patients. Members of these diverse and dynamic communities can be thought of as pathogens, benign commensals, or synergens — organisms not considered pathogens in the traditional sense but with the capacity to alter the pathogenesis of the community through microbe–microbe or polymicrobe–host interactions. Very few bacterial pathogens have been implicated as clinically relevant in CF; however, the CF airway microbiome can be a reservoir of previously unrecognized but clinically relevant organisms. A combination of culture-dependent and culture-independent approaches provides a more comprehensive perspective of CF microbiology than either approach alone. Here we review these concepts, highlight the future challenges for CF microbiology, and discuss the implications for the management of CF airway infections. We suggest that the success of treatment interventions for chronic CF lung disease will rely on the context of the microbes within microbial communities. The microbiology of CF airways may serve as a model to investigate the emergent properties of other clinically relevant microbial communities in the human body.

scholarly journals Cystic Fibrosis Airway Microbiome: Overturning the Old, Opening the Way for the New

2017 ◽  
Vol 200 (4) ◽  
Author(s):  
George A. O'Toole
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Chronic Infections ◽  
Cystic Fibrosis Airway ◽  
Airway Infections ◽  
Culture Independent ◽  
Airway Microbiome ◽  
New Strategies ◽  
The Way

ABSTRACTThe genetic disease cystic fibrosis (CF) is associated with chronic airway infections that are a proximal cause of death in many patients with this affliction. Classic microbiology studies focusing on canonical pathogens resulted in the development of a common set of views regarding the nature of the airway infections associated with this disease, and these ideas have influenced everything from the way infections are treated to how clinical trials for new CF-targeted antibiotics are designed and the focus of CF-related research topics. Recent culture-independent studies have prompted us to rethink, and in some cases discard, some of these long-held views. In this piece, I argue that an updated view of the complicated chronic infections associated with CF, thanks in large part to culture-independent studies of sputum and bronchoalveolar lavage fluid samples, should be leveraged to develop new strategies to treat these recalcitrant infections.

scholarly journals One versus Many: Polymicrobial Communities and the Cystic Fibrosis Airway

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Fabrice Jean-Pierre ◽  
Arsh Vyas ◽  
Thomas H. Hampton ◽  
Michael A. Henson ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Species Interactions ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Community Function ◽  
Cystic Fibrosis Airway ◽  
Airway Infections ◽  
Culture Independent ◽  
Polymicrobial Communities

ABSTRACT Culture-independent studies have revealed that chronic lung infections in persons with cystic fibrosis (pwCF) are rarely limited to one microbial species. Interactions among bacterial members of these polymicrobial communities in the airways of pwCF have been reported to modulate clinically relevant phenotypes. Furthermore, it is clear that a single polymicrobial community in the context of CF airway infections cannot explain the diversity of clinical outcomes. While large 16S rRNA gene-based studies have allowed us to gain insight into the microbial composition and predicted functional capacities of communities found in the CF lung, here we argue that in silico approaches can help build clinically relevant in vitro models of polymicrobial communities that can in turn be used to experimentally test and validate computationally generated hypotheses. Furthermore, we posit that combining computational and experimental approaches will enhance our understanding of mechanisms that drive microbial community function and identify new therapeutics to target polymicrobial infections.

scholarly journals Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Buqing Yi ◽  
Alexander H. Dalpke ◽  
Sébastien Boutin
Keyword(s):  
Cystic Fibrosis ◽  
Essential Role ◽  
Genetic Defect ◽  
Limiting Factors ◽  
Major Life ◽  
Treatment Scheme ◽  
Cystic Fibrosis Airway ◽  
Airway Infections ◽  
Airway Microbiome ◽  
Airway Physiology

The development of CFTR modulator therapies significantly changed the treatment scheme of people with cystic fibrosis. However, CFTR modulator therapy is still a life-long treatment, which is not able to correct the genetic defect and cure the disease. Therefore, it becomes crucial to understand the effects of such modulation of CFTR function on the airway physiology, especially on airway infections and inflammation that are currently the major life-limiting factors in people with cystic fibrosis. In this context, understanding the dynamics of airway microbiome changes in response to modulator therapy plays an essential role in developing strategies for managing airway infections. Whether and how the newly available therapies affect the airway microbiome is still at the beginning of being deciphered. We present here a brief review summarizing the latest information about microbiome alterations in light of modern cystic fibrosis modulator therapy.

scholarly journals Cystic fibrosis microbiome: analysis of nasal middle meatus and sputum in different lung disease stages

2020 ◽  
Vol 3 (3) ◽  
pp. 225-237
Author(s):  
F.G.O. Maestrali ◽  
R.R.M. Pilan ◽  
R. Athanazio ◽  
L.G. Sparvoli ◽  
R.V. Cortez ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Advanced Disease ◽  
Respiratory Infections ◽  
Middle Meatus ◽  
Culture Methods ◽  
Microbiome Composition ◽  
Conventional Culture ◽  
Culture Independent ◽  
Airway Microbiome

BACKGROUND: Culture independent methods of molecular detection of microbiome have shown the polymicrobial nature of respiratory infections in cystic fibrosis, with pathogenic agents undetectable in conventional culture methods. Composition and diversity of the airway microbiome are still poorly understood. METHODOLOGY: This study evaluated the airway microbiome in 31 adult cystic fibrosis patients via the analysis of 16S rRNA se- quences by next generation sequencing. RESULTS: Staphylococcus, Streptococcus and Corynebacterium were the most abundant genera in the middle meatus, and Pseudo- monas, Haemophilus and Prevotella were the most abundant in sputum. In patients with advanced disease (FEV1< 50%), there was an increase in the prevalence of Pseudomonas in both sample types when studied separately. In each patient, in a paired analysis, the sputum and middle meatus showed similar microbiome composition in mild or moderate disease (FEV1≥ 50%). In patients with severe lung disease, the relative abundance of Pseudomonas had a positive correlation in both collection sites. CONCLUSIONS: This is the first Brazilian study to evaluate the airway microbiome in cystic fibrosis patients. Our findings agree with those in the international literature and indicate the role of Pseudomonas in the sputum and middle meatus in patients with advanced disease.

scholarly journals Microbiology of Cystic Fibrosis Airway Disease

2019 ◽  
Vol 40 (06) ◽  
pp. 727-736 ◽  
Author(s):  
Ana C. Blanchard ◽  
Valerie J. Waters
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Treatment Options ◽  
Airway Disease ◽  
Burkholderia Cepacia Complex ◽  
Pulmonary Infections ◽  
Lung Function Decline ◽  
Cystic Fibrosis Airway ◽  
Airway Infections ◽  
Culture Independent

AbstractAlthough survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and species of the Burkholderia cepacia complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.

scholarly journals The Role of Lower Airway Dysbiosis in Asthma: Dysbiosis and Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Junying Lu ◽  
Lingxin Xiong ◽  
Xiaohao Zhang ◽  
Zhongmin Liu ◽  
Shiji Wang ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Chronic Respiratory Disease ◽  
Lower Airway ◽  
Healthy Controls ◽  
Steroid Resistant ◽  
Lung Microbiome ◽  
Culture Independent ◽  
Airway Microbiome ◽  
New Evidence

With the development of culture-independent techniques, numerous studies have demonstrated that the lower airway is not sterile in health and harbors diverse microbial communities. Furthermore, new evidence suggests that there is a distinct lower airway microbiome in those with chronic respiratory disease. To understand the role of lower airway dysbiosis in the pathogenesis of asthma, in this article, we review the published reports about the lung microbiome of healthy controls, provide an outlook on the contribution of lower airway dysbiosis to asthma, especially steroid-resistant asthma, and discuss the potential therapies targeted for lower airway dysbiosis.

scholarly journals Exposing the Three-Dimensional Biogeography and Metabolic States of Pathogens in Cystic Fibrosis Sputum via Hydrogel Embedding, Clearing, and rRNA Labeling

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
William H. DePas ◽  
Ruth Starwalt-Lee ◽  
Lindsey Van Sambeek ◽  
Sripriya Ravindra Kumar ◽  
Viviana Gradinaru ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Growth Rate ◽  
Microbial Communities ◽  
Spatial Organization ◽  
Single Cells ◽  
Host Cells ◽  
Individual Species ◽  
Complex Environments ◽  
Host Interactions

ABSTRACT Physiological resistance to antibiotics confounds the treatment of many chronic bacterial infections, motivating researchers to identify novel therapeutic approaches. To do this effectively, an understanding of how microbes survive in vivo is needed. Though much can be inferred from bulk approaches to characterizing complex environments, essential information can be lost if spatial organization is not preserved. Here, we introduce a tissue-clearing technique, termed MiPACT, designed to retain and visualize bacteria with associated proteins and nucleic acids in situ on various spatial scales. By coupling MiPACT with hybridization chain reaction (HCR) to detect rRNA in sputum samples from cystic fibrosis (CF) patients, we demonstrate its ability to survey thousands of bacteria (or bacterial aggregates) over millimeter scales and quantify aggregation of individual species in polymicrobial communities. By analyzing aggregation patterns of four prominent CF pathogens, Staphylococcus aureus , Pseudomonas aeruginosa , Streptococcus sp., and Achromobacter xylosoxidans , we demonstrate a spectrum of aggregation states: from mostly single cells ( A. xylosoxidans ), to medium-sized clusters ( S. aureus ), to a mixture of single cells and large aggregates ( P. aeruginosa and Streptococcus sp.). Furthermore, MiPACT-HCR revealed an intimate interaction between Streptococcus sp. and specific host cells. Lastly, by comparing standard rRNA fluorescence in situ hybridization signals to those from HCR, we found that different populations of S. aureus and A. xylosoxidans grow slowly overall yet exhibit growth rate heterogeneity over hundreds of microns. These results demonstrate the utility of MiPACT-HCR to directly capture the spatial organization and metabolic activity of bacteria in complex systems, such as human sputum. IMPORTANCE The advent of metagenomic and metatranscriptomic analyses has improved our understanding of microbial communities by empowering us to identify bacteria, calculate their abundance, and profile gene expression patterns in complex environments. We are still technologically limited, however, in regards to the many questions that bulk measurements cannot answer, specifically in assessing the spatial organization of microbe-microbe and microbe-host interactions. Here, we demonstrate the power of an enhanced optical clearing method, MiPACT, to survey important aspects of bacterial physiology (aggregation, host interactions, and growth rate), in situ , with preserved spatial information when coupled to rRNA detection by HCR. Our application of MiPACT-HCR to cystic fibrosis patient sputum revealed species-specific aggregation patterns, yet slow growth characterized the vast majority of bacterial cells regardless of their cell type. More broadly, MiPACT, coupled with fluorescent labeling, promises to advance the direct study of microbial communities in diverse environments, including microbial habitats within mammalian systems.

The Fungal Airway Microbiome in Cystic Fibrosis and Bronchiectasis

2020 ◽  
Author(s):  
Leah Cuthbertson ◽  
Imogen Felton ◽  
Phillip James ◽  
Michael J. Cox ◽  
Diana Bilton ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Microbiome

scholarly journals The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis

2020 ◽  
Author(s):  
Leah Cuthbertson ◽  
Imogen Felton ◽  
Phillip James ◽  
Michael J. Cox ◽  
Diana Bilton ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Microbiome

scholarly journals Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 766
Author(s):  
David F. Woods ◽  
Stephanie Flynn ◽  
Jose A. Caparrós-Martín ◽  
Stephen M. Stick ◽  
F. Jerry Reen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bile Acids ◽  
Host Response ◽  
Signal Molecules ◽  
Therapeutic Approaches ◽  
Related Factors ◽  
Host Interactions ◽  
Important Host ◽  
Respiratory Microbiota

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation–pathogen–host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease.

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