Detection of Anaerobic Bacteria in High Numbers in Sputum from Patients with Cystic Fibrosis

Tunney, Michael; Field, Tyler R.; Moriarty, T. Fintan; Patrick, Sheila; Doering, G.; Muhlebach, Marianne S.; Wolfgang, Matthew C.; Boucher, Richard C.; Gilpin, D.F.; McDowell, Andrew; Elborn, J. Stuart

doi:10.1164/rccm.200708-1151oc

Cited by 429 publications

(427 citation statements)

References 57 publications

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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.…”

Section: Sources Of the Fermentative Responsesupporting

confidence: 57%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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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.

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Section: Sources Of the Fermentative Responsesupporting

confidence: 57%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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“…Conventional bacterial culture in aerobic conditions allows isolation of a limited number of organisms. Extended culture methods identify a much wider range of bacteria, which include more difficult to culture bacteria, such as anaerobic bacteria (4,15,23). At present, there is no readily available methodology to identify all of these organisms in a way that makes this information valuable for clinical treatment (77).…”

Section: Treating Multiple Infectionsmentioning

confidence: 99%

“…However, many bacteria form biofilms in the CF lung that make their eradication difficult (3). In addition, it has also become clear that only a small fraction of the microbes present in the CF airway are being identified with routine laboratory techniques (4,5), and both extended culture methods and molecular techniques have identified organisms that previously were not routinely cultured (6). Traditional antibiotic susceptibility testing performed on planktonic bacteria has been found to be of limited clinical use in chronic airway infection as most bacteria in the CF lung exist in biofilms (7).…”

mentioning

confidence: 99%

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

et al. 2014

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Despite significant advances in treatment strategies targeting the underlying defect in cystic fibrosis (CF), airway infection remains an important cause of lung disease. In this two-part series, we review recent evidence related to the complexity of CF airway infection, explore data suggesting the relevance of individual microbial species, and discuss current and future treatment options. In Part I, the evidence with respect to the spectrum of bacteria present in the CF airway, known as the lung microbiome is discussed. Subsequently, the current approach to treat methicillin-resistant Staphylococcus aureus, gram-negative bacteria, as well as multiple coinfections is reviewed. Newer molecular techniques have demonstrated that the airway microbiome consists of a large number of microbes, and the balance between microbes, rather than the mere presence of a single species, may be relevant for disease pathophysiology. A better understanding of this complex environment could help define optimal treatment regimens that target pathogens without affecting others. Although relevance of these organisms is unclear, the pathologic consequences of methicillin-resistant S. aureus infection in patients with CF have been recently determined. New strategies for eradication and treatment of both acute and chronic infections are discussed. Pseudomonas aeruginosa plays a prominent role in CF lung disease, but many other nonfermenting gram-negative bacteria are also found in the CF airway. Many new inhaled antibiotics specifically targeting P. aeruginosa have become available with the hope that they will improve the quality of life for patients. Part I concludes with a discussion of how best to treat patients with multiple coinfections.

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“…Notably, obligately anaerobic taxa have gained recent attention for their abundance in expectorated sputum, bronchoalveolar lavage fluid and explanted lungs [5,27,28,[32][33][34]. A role for these organisms in CF disease has not yet been established; however, some have been characterized for their ability to degrade and ferment salivary mucins in the oral cavity [21,23,35].…”

Section: Saliva-derived Mucin-fermenting Bacteria Support the Growth mentioning

confidence: 99%

Evidence and role for bacterial mucin degradation in cystic fibrosis airway disease

Flynn

Niccum

Dunitz

et al. 2016

Preprint

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Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. Author SummaryPersistent CF lung infections are composed of hundreds of microbial taxa whose interactions contribute to respiratory failure. Despite their importance, the complex interplay between the lung microbiota and host environment is poorly understood. For example, the nutrients that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. We reveal that a subset of CF microbiota is capable of fermenting mucins for carbon and energy which, in-turn, can support the carbon demands of other PLOS Pathogens |

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Detection of Anaerobic Bacteria in High Numbers in Sputum from Patients with Cystic Fibrosis

Cited by 429 publications

References 57 publications

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

Evidence and role for bacterial mucin degradation in cystic fibrosis airway disease

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