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

Quinn, Robert A.; Whiteson, Katrine; Lim, Yan-Wei; Salamon, Peter; Bailey, Barbara; Mienardi, Simone; Sanchez, Savannah E.; Blake, Donald R.; Conrad, Doug; Rohwer, Forest

doi:10.1038/ismej.2014.266

Cited by 15 publications

(17 citation statements)

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“…The signal for a reduction in microbial diversity and anaerobe abundance during antibiotic treatment supports previously described changes in a large cross-sectional study (5) and in vitro experiments (4). Thus, there is mounting evidence for changes between classic pathogens and anaerobic bacteria around CFPE events (4,5,13). However, our data also showed microbiome and metabolome dynamics during times of stability which was, at least in part, driven by maintenance antibiotics.…”

Section: Discussionmentioning

confidence: 52%

“…During the development of a pulmonary exacerbation, there was an increase in microbial diversity corresponding to a relative increase of the ratio of anaerobes to pathogens, which then decreased during treatment. Thus, dynamics between classic pathogens and anaerobic bacteria around CFPE events may be important for therapeutic outcomes (4,5,10). Future studies that target CFPE therapy in a systematic manner are needed, particularly when the same antibiotic is repeatedly provided, to determine if any of the observed dynamics are predictable and if the reduction in anaerobe abundance during treatment corresponds to positive clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that pathogens come to dominate the community profiles as subjects age and microbial diversity decreases (1), yet we have a poor understanding of these dynamics in shorter longitudinal time frames, such as throughout CF pulmonary exacerbations (CFPEs). Some studies have reported changes occurring during CFPE (4)(5)(6)(7)(8)(9), primarily via reduction in the relative abundance of rare taxa during treatment, particularly anaerobic bacteria (Prevotella, Veillonella, Gemella, etc.) (4, 5, 9-11), but whether this represents a dysbiotic shift in the CF microbiome or regular changes in microbial dynamics without clinical relevance remains unknown.…”

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confidence: 99%

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High-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic Therapy

et al. 2020

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Microbial diversity in the cystic fibrosis (CF) lung decreases over decades as pathogenic bacteria such as Pseudomonas aeruginosa take over. The dynamics of the CF microbiome and metabolome over shorter time frames, however, remain poorly studied. Here, we analyze paired microbiome and metabolome data from 594 sputum samples collected over 401 days from six adult CF subjects (subject mean = 179 days) through periods of clinical stability and 11 CF pulmonary exacerbations (CFPE). While microbiome profiles were personalized (permutational multivariate analysis of variance [PERMANOVA] r2 = 0.79, P < 0.001), we observed significant intraindividual temporal variation that was highest during clinical stability (linear mixed-effects [LME] model, P = 0.002). This included periods where the microbiomes of different subjects became highly similar (UniFrac distance, <0.05). There was a linear increase in the microbiome alpha-diversity and in the log ratio of anaerobes to pathogens with time (n = 14 days) during the development of a CFPE (LME P = 0.0045 and P = 0.029, respectively). Collectively, comparing samples across disease states showed there was a reduction of these two measures during antibiotic treatment (LME P = 0.0096 and P = 0.014, respectively), but the stability data and CFPE data were not significantly different from each other. Metabolome alpha-diversity was higher during CFPE than during stability (LME P = 0.0085), but no consistent metabolite signatures of CFPE across subjects were identified. Virulence-associated metabolites from P. aeruginosa were temporally dynamic but were not associated with any disease state. One subject died during the collection period, enabling a detailed look at changes in the 194 days prior to death. This subject had over 90% Pseudomonas in the microbiome at the beginning of sampling, and that level gradually increased to over 99% prior to death. This study revealed that the CF microbiome and metabolome of some subjects are dynamic through time. Future work is needed to understand what drives these temporal dynamics and if reduction of anaerobes correlate to clinical response to CFPE therapy. IMPORTANCE Subjects with cystic fibrosis battle polymicrobial lung infections throughout their lifetime. Although antibiotic therapy is a principal treatment for CF lung disease, we have little understanding of how antibiotics affect the CF lung microbiome and metabolome and how much the community changes on daily timescales. By analyzing 594 longitudinal CF sputum samples from six adult subjects, we show that the sputum microbiome and metabolome are dynamic. Significant changes occur during times of stability and also through pulmonary exacerbations (CFPEs). Microbiome alpha-diversity increased as a CFPE developed and then decreased during treatment in a manner corresponding to the reduction in the log ratio of anaerobic bacteria to classic pathogens. Levels of metabolites from the pathogen P. aeruginosa were also highly variable through time and were negatively associated with anaerobes. The microbial dynamics observed in this study may have a significant impact on the outcome of antibiotic therapy for CFPEs and overall subject health.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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High-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic Therapy

et al. 2020

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“…To test the hypothesis that different ASM formulations would result in differential production of P. aeruginosa specialized metabolites, strain PAO1 was statically cultured in nine different ASM formulations. [3][4][5][6][7][8]10,11 We chose the nine ASM formulations based upon citation count, prior use in our research, and if the formulation was a predecessor to other formulations. Broadly, these ASM can be separated into two lineages, complex and chemically defined.…”

mentioning

confidence: 99%

“…Soothill ASM was created using literature values for key nutrients identified in CF sputum, taking into account economic cost of materials. 4 This base medium was modified by other researchers by addition of amino acids 6,9,10 , bovine serum albumin (BSA) 6 , alterations of mucin 3,8 and DNA 3 concentration, and replacement of amino acid 5,8 or iron source. 5 Concurrent to the development of the complex ASM lineage, the chemically defined synthetic CF medium (SCFM) series of ASM was created from the average concentrations of ions, free amino acids, glucose, and lactate measured from CF sputum samples (Figure 1).…”

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confidence: 99%

Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

Phelan

2021

Preprint

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Artificial sputum medium (ASM) is a class of in vitro bacterial culture medium intended to mimic the nutritional environment of cystic fibrosis (CF) pulmonary mucus. One of the most commonly studied microbes in ASM is Pseudomonas aeruginosa, a prevalent and dangerous pathogen of the CF pulmonary microbiome. Many ASM formulations have been reported in literature, with differing nutrient concentrations and availability. Here, we show that common formulations of ASM yield different phenotypes and chemotypes of P. aeruginosa. Further, we demonstrate that iron in commercial porcine gastric mucin (PGM) is sufficient to alter production of P. aeruginosa siderophores in the chemically defined ASM, synthetic CF medium 1 (SCFM1). These results highlight that the choice of ASM formulation for in vitro investigations of microbial pathogenicity, physiology, and interactions should be carefully considered.IMPORTANCEIn vitro culture media are being developed to resemble the in vivo nutritional environment more closely. These culture media are used to investigate microbial pathogenicity and ecology in environments that are more reflective of disease states. In cystic fibrosis (CF), a number of different artificial sputum media (ASM) formulations have been created to recapitulate the CF lung environment. However, these ASM have different sources and concentrations of nutrients. Here, we cultured Pseudomonas aeruginosa in nine different formulations of ASM. P. aeruginosa is the primary pathogen causing lung infection in CF.We show that different ASM formulations lead to different phenotypes and chemotypes by P. aeruginosa and one component of ASM, mucin, contains high levels of iron, which may affect P. aeruginosa physiology.

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Cystic fibrosis lung microbiome: Opportunities to reconsider management of airway infection

Caverly

Zhao

LiPuma

2015

Pediatric Pulmonology

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Summary. The importance of infection in the pathogenesis of cystic fibrosis (CF) lung disease has been long recognized, and the use of antibiotics targeting bacteria identified in cultures of respiratory specimens has played a critical role in improving outcomes for individuals with CF. Over the past $15 years, the use of culture-independent methods to assess airway microbiology in CF has revealed complex and dynamic CF airway bacterial communities. Recent areas of investigation of the CF lung microbiome have included exploring how bacterial community structures change over time, particularly with respect to disease progression or pulmonary exacerbation, and in response to antibiotic therapies. This review will discuss what has been learned from these studies as well as how these findings offer opportunities to further refine management of CF airway infection. Pediatr Pulmonol. 2015;50:S31-S38.

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

Cited by 15 publications

References 0 publications

High-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic Therapy

High-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic Therapy

Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

Cystic fibrosis lung microbiome: Opportunities to reconsider management of airway infection

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