10 results on '"Bruce, Kenneth"'
Search Results
2. Staphylococcus aureus Small-Colony Variants Are Independently Associated With Worse Lung Disease in Children With Cystic Fibrosis
- Author
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Wolter, Daniel J., Emerson, Julia C., McNamara, Sharon, Buccat, Anne M., Qin, Xuan, Cochrane, Elizabeth, Houston, Laura S., Rogers, Geraint B., Marsh, Peter, Prehar, Karandeep, Pope, Christopher E., Blackledge, Marcella, Déziel, Eric, Bruce, Kenneth D., Ramsey, Bonnie W., Gibson, Ronald L., Burns, Jane L., and Hoffman, Lucas R.
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- 2013
- Full Text
- View/download PDF
3. Enhancing the utility of existing antibiotics by targeting bacterial behaviour?
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Rogers, Geraint B, Carroll, Mary P, and Bruce, Kenneth D
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ANTIBIOTICS ,TARGETED drug delivery ,DRUG development ,DRUG resistance ,DISEASE susceptibility ,BACTERIAL diseases ,BIOFILMS - Abstract
The discovery of novel classes of antibiotics has slowed dramatically. This has occurred during a time when the appearance of resistant strains of bacteria has shown a substantial increase. Concern is therefore mounting over our ability to continue to treat infections in an effective manner using the antibiotics that are currently available. While ongoing efforts to discover new antibiotics are important, these must be coupled with strategies that aim to maintain as far as possible the spectrum of activity of existing antibiotics. In many instances, the resistance to antibiotics exhibited by bacteria in chronic infections is mediated not by direct resistance mechanisms, but by the adoption of modes of growth that confer reduced susceptibility. These include the formation of biofilms and the occurrence of subpopulations of 'persister' cells. As our understanding of these processes has increased, a number of new potential drug targets have been revealed. Here, advances in our ability to disrupt these systems that confer reduced susceptibility, and in turn increase the efficacy of antibiotic therapy, are discussed. [ABSTRACT FROM AUTHOR]
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- 2012
- Full Text
- View/download PDF
4. Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities.
- Author
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van der Gast, Christopher J, Walker, Alan W, Stressmann, Franziska A, Rogers, Geraint B, Scott, Paul, Daniels, Thomas W, Carroll, Mary P, Parkhill, Julian, and Bruce, Kenneth D
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CYSTIC fibrosis ,LUNG microbiology ,BACTERIAL diseases ,PSEUDOMONAS aeruginosa ,RNA ,BACTERIAL diversity ,ANTIBIOTICS ,BACTERIAL cultures - Abstract
Cystic fibrosis (CF) patients suffer from chronic bacterial lung infections that lead to death in the majority of cases. The need to maintain lung function in these patients means that characterising these infections is vital. Increasingly, culture-independent analyses are expanding the number of bacterial species associated with CF respiratory samples; however, the potential significance of these species is not known. Here, we applied ecological statistical tools to such culture-independent data, in a novel manner, to partition taxa within the metacommunity into core and satellite species. Sputa and clinical data were obtained from 14 clinically stable adult CF patients. Fourteen rRNA gene libraries were constructed with 35 genera and 82 taxa, identified in 2139 bacterial clones. Shannon-Wiener and taxa-richness analyses confirmed no undersampling of bacterial diversity. By decomposing the distribution using the ratio of variance to the mean taxon abundance, we partitioned objectively the species abundance distribution into core and satellite species. The satellite group comprised 67 bacterial taxa from 33 genera and the core group, 15 taxa from 7 genera (including Pseudomonas (1 taxon), Streptococcus (2), Neisseria (2), Catonella (1), Porphyromonas (1), Prevotella (5) and Veillonella (3)], the last four being anaerobes). The core group was dominated by Pseudomonas aeruginosa. Other recognised CF pathogens were rare. Mantel and partial Mantel tests assessed which clinical factors influenced the composition observed. CF transmembrane conductance regulator genotype and antibiotic treatment correlated with all core taxa. Lung function correlated with richness. The clinical significance of these core and satellite species findings in the CF lung is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
5. Lung function and microbiota diversity in cystic fibrosis
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Cuthbertson, Leah, Walker, Alan W., Oliver, Anna E., Rogers, Geraint B., Rivett, Damian W., Hampton, Thomas H., Ashare, Alix, Elborn, J. Stuart, De Soyza, Anthony, Carroll, Mary P., Hoffman, Lucas R., Lanyon, Clare, Moskowitz, Samuel M., O’Toole, George A., Parkhill, Julian, Planet, Paul J., Teneback, Charlotte C., Tunney, Michael M., Zuckerman, Jonathan B., Bruce, Kenneth D., and Van Der Gast, Christopher J.
- Subjects
Biogeography ,Antibiotics ,Research ,Microbial surveillance ,Lung microbiota ,respiratory system ,Disease severity ,Cystic fibrosis ,Lung function ,Lung microbiome ,respiratory tract diseases ,3. Good health ,Ecological patterns - Abstract
Background: Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF. Results: We tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa. Conclusions: Our findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF. BBFJdPr3cu-jH3LTAhe361Video Abstract
6. Lung function and microbiota diversity in cystic fibrosis
- Author
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Cuthbertson, Leah, Walker, Alan W, Oliver, Anna E, Rogers, Geraint B, Rivett, Damian W, Hampton, Thomas H, Ashare, Alix, Elborn, J Stuart, De Soyza, Anthony, Carroll, Mary P, Hoffman, Lucas R, Lanyon, Clare, Moskowitz, Samuel M, O'Toole, George A, Parkhill, Julian, Planet, Paul J, Teneback, Charlotte C, Tunney, Michael M, Zuckerman, Jonathan B, Bruce, Kenneth D, and Van Der Gast, Christopher J
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Adult ,Male ,Cystic Fibrosis ,Lung microbiome ,Ecological patterns ,Young Adult ,Antibiotics ,Microbial surveillance ,Humans ,Disease severity ,Lung ,Inflammation ,Bacteria ,Microbiota ,Sputum ,Sequence Analysis, DNA ,respiratory system ,Lung function ,United States ,respiratory tract diseases ,3. Good health ,Anti-Bacterial Agents ,Respiratory Function Tests ,Europe ,Biogeography ,Disease Progression ,Lung microbiota ,Female - Abstract
BACKGROUND: Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF. RESULTS: We tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa. CONCLUSIONS: Our findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF. Video Abstract.
7. Lung function and microbiota diversity in cystic fibrosis
- Author
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Cuthbertson, Leah, Walker, Alan W., Oliver, Anna E., Rogers, Geraint B., Rivett, Damian W., Hampton, Thomas H., Ashare, Alix, Elborn, J. Stuart, De Soyza, Anthony, Carroll, Mary P., Hoffman, Lucas R., Lanyon, Clare, Moskowitz, Samuel M., O’Toole, George A., Parkhill, Julian, Planet, Paul J., Teneback, Charlotte C., Tunney, Michael M., Zuckerman, Jonathan B., Bruce, Kenneth D., and Van Der Gast, Christopher J.
- Subjects
Biogeography ,Antibiotics ,Research ,Microbial surveillance ,Lung microbiota ,respiratory system ,Disease severity ,Cystic fibrosis ,Lung function ,Lung microbiome ,respiratory tract diseases ,3. Good health ,Ecological patterns - Abstract
Background: Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF. Results: We tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa. Conclusions: Our findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF. Video Abstract
8. The impact of azithromycin therapy on the airway microbiota in asthma.
- Author
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Slater, Mariel, Rivett, Damian W., Williams, Lisa, Martin, Matthew, Harrison, Tim, Sayers, Ian, Bruce, Kenneth D., and Shaw, Dominick
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AZITHROMYCIN ,AIRWAY (Anatomy) ,ASTHMA treatment ,MACROLIDE antibiotics ,NEUTROPHILS ,ANTIBIOTICS ,THERAPEUTICS - Abstract
The article focuses on a study on the impact of azithromycin therapy on the airway microbiota in asthma, as of July 2014. Topics include an improvement in airway hyperresponsiveness (AHR) and measures of airway inflammation through macrolides, the association of Azithromycin therapy with decreased bacterial richness in the airways and the impact of Azithromycin in the reduction of mucus secretion, airway neutrophil accumulation and antibiotic and antipseudomonal activity.
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- 2014
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9. Interpreting infective microbiota: the importance of an ecological perspective.
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Rogers, Geraint B., Hoffman, Lucas R., Carroll, Mary P., and Bruce, Kenneth D.
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ANTIBIOTICS , *CONIFERS , *CYSTIC fibrosis , *LUNG infections , *MOLECULAR biology , *MICROBIOLOGY , *GUT microbiome - Abstract
Highlights: [•] Interpreting complex microbiota in infective contexts is a pressing challenge. [•] Potentially, associations can be interpreted spuriously as causal. [•] We argue for the need to include ecological theory in clinical interpretation. [•] Cystic fibrosis lung infections are used as an illustrative model system. [Copyright &y& Elsevier]
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- 2013
- Full Text
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10. Revealing the dynamics of polymicrobial infections: implications for antibiotic therapy
- Author
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Rogers, Geraint B., Hoffman, Lucas R., Whiteley, Marvin, Daniels, Thomas W.V., Carroll, Mary P., and Bruce, Kenneth D.
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BIOTIC communities , *CYSTIC fibrosis , *RESPIRATORY diseases , *TREATMENT effectiveness , *COMMUNICABLE disease treatment , *ANTIBIOTICS , *DISEASE management ,INFECTION treatment - Abstract
As a new generation of culture-independent analytical strategies emerge, the amount of data on polymicrobial infections will increase dramatically. For these data to inform clinical thinking, and in turn to maximise benefits for patients, an appropriate framework for their interpretation is required. Here, we use cystic fibrosis (CF) lower airway infections as a model system to examine how conceptual and technological advances can address two clinical questions that are central to improved management of CF respiratory disease. Firstly, can markers of the microbial community be identified that predict a change in infection dynamics and clinical outcomes? Secondly, can these new strategies directly characterize the impact of antimicrobial therapies, allowing treatment efficacy to be both assessed and optimized? [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
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