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 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 Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms

2015 ◽  
Vol 60 (1) ◽  
pp. 348-355 ◽  
Author(s):  
Sarah Kennedy ◽  
Trevor Beaudoin ◽  
Yvonne C. W. Yau ◽  
Emma Caraher ◽  
James E. A. Zlosnik ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Suppressive Therapy ◽  
High Dose ◽  
Lung Function Decline ◽  
Complex Species ◽  
Content Type ◽  
Biofilm Thickness

ABSTRACTPulmonary infection withBurkholderia cepaciacomplex in cystic fibrosis (CF) patients is associated with more-rapid lung function decline and earlier death than in CF patients without this infection. In this study, we used confocal microscopy to visualize the effects of various concentrations of tobramycin, achievable with systemic and aerosolized drug administration, on matureB. cepaciacomplex biofilms, both in the presence and absence of CF sputum. After 24 h of growth, biofilm thickness was significantly reduced by exposure to 2,000 μg/ml of tobramycin forBurkholderia cepacia,Burkholderia multivorans, andBurkholderia vietnamiensis; 200 μg/ml of tobramycin was sufficient to reduce the thickness ofBurkholderia dolosabiofilm. With a more mature 48-h biofilm, significant reductions in thickness were seen with tobramycin at concentrations of ≥100 μg/ml for allBurkholderiaspecies. In addition, an increased ratio of dead to live cells was observed in comparison to control with tobramycin concentrations of ≥200 μg/ml forB. cepaciaandB. dolosa(24 h) and ≥100 μg/ml forBurkholderia cenocepaciaandB. dolosa(48 h). Although sputum significantly increased biofilm thickness, tobramycin concentrations of 1,000 μg/ml were still able to significantly reduce biofilm thickness of allB. cepaciacomplex species with the exception ofB. vietnamiensis. In the presence of sputum, 1,000 μg/ml of tobramycin significantly increased the dead-to-live ratio only forB. multivoranscompared to control. In summary, although killing is attenuated, high-dose tobramycin can effectively decrease the thickness ofB. cepaciacomplex biofilms, even in the presence of sputum, suggesting a possible role as a suppressive therapy in CF.

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 Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients

2021 ◽  
Vol 10 (6) ◽  
pp. 1275
Author(s):  
Anna Engell Holm ◽  
Hans Henrik Lawaetz Schultz ◽  
Helle Krogh Johansen ◽  
Tania Pressler ◽  
Thomas Kromann Lund ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplantation ◽  
Burkholderia Cepacia ◽  
Bacterial Species ◽  
Positive Culture ◽  
Burkholderia Cepacia Complex ◽  
Achromobacter Xylosoxidans ◽  
Lung Function Decline ◽  
Before And After ◽  
The Impact

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1–91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

scholarly journals Direct Culture-Independent Strain Typing of Burkholderia cepacia Complex in Sputum Samples from Patients with Cystic Fibrosis

2010 ◽  
Vol 48 (5) ◽  
pp. 1888-1891 ◽  
Author(s):  
P. Drevinek ◽  
S. Vosahlikova ◽  
K. Dedeckova ◽  
O. Cinek ◽  
E. Mahenthiralingam
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Burkholderia Cepacia Complex ◽  
Strain Typing ◽  
Culture Independent

scholarly journals Cystic Fibrosis Sputum Impairs the Ability of Neutrophils to Kill Staphylococcus aureus

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 703
Author(s):  
Kayla Fantone ◽  
Samantha L. Tucker ◽  
Arthur Miller ◽  
Ruchi Yadav ◽  
Eryn E. Bernardy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Healthy Volunteers ◽  
Airway Disease ◽  
Neutrophil Extracellular Trap ◽  
Lung Function Decline ◽  
Bacterial Killing ◽  
Cystic Fibrosis Sputum ◽  
Microbial Infections

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. Staphylococcus aureus (S. aureus) is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill S. aureus, it remains largely unknown why PMNs fail to eliminate S. aureus in CF. The goal of this study was to observe how the CF airway environment affects S. aureus killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of S. aureus were obtained from the airways of CF patients. The results show that PMNs from healthy volunteers were able to kill all CF isolates and laboratory strains of S. aureus tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, S. aureus killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing S. aureus. Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of S. aureus was not diminished. The S. aureus-induced respiratory burst and neutrophil extracellular trap release from PMNs also remained uninhibited by CF sputum. In summary, our data demonstrate that the CF airway environment limits killing of S. aureus by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.

Clonal diversity among Burkholderia cepacia complex isolates from cystic fibrosis patients in a reference unit

2013 ◽  
Vol 31 (10) ◽  
pp. 665-668 ◽  
Author(s):  
Laura Barrado ◽  
M. Teresa Martinez ◽  
Jennifer Villa ◽  
M. Ángeles Orellana ◽  
Esther Viedma ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Clonal Diversity ◽  
Burkholderia Cepacia Complex

scholarly journals Differential Persistence among Genomovars of the Burkholderia cepacia Complex in a Murine Model of Pulmonary Infection

2002 ◽  
Vol 70 (5) ◽  
pp. 2715-2720 ◽  
Author(s):  
Karen K. Chu ◽  
Donald J. Davidson ◽  
T. Keith Halsey ◽  
Jacqueline W. Chung ◽  
David P. Speert
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Outcomes ◽  
Murine Model ◽  
Burkholderia Cepacia ◽  
Pulmonary Infection ◽  
Burkholderia Cepacia Complex ◽  
Clinical Infection ◽  
Minimal Toxicity

ABSTRACT Cystic fibrosis patients infected with strains from different genomovars of the Burkholderia cepacia complex can experience diverse clinical outcomes. To identify genomovar-specific determinants that might be responsible for these differences, we developed a pulmonary model of infection in BALB/c mice. Mice were rendered leukopenic by administration of cyclophosphamide prior to intranasal challenge with 1.6 × 104 bacteria. Five of six genomovar II strains persisted at stable numbers in the lungs until day 16 with minimal toxicity, whereas zero of seven genomovar III strains persisted but resulted in variable toxicity. We have developed a chronic pulmonary model of B. cepacia infection which reveals differences among genomovars in terms of clinical infection outcome.

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