Mucoid and Nonmucoid <i>Burkholderia cepacia</i> Complex Bacteria in Cystic Fibrosis Infections

Zlosnik, James E. A.; Costa, Paulo Sucasas; Brant, Rollin; Mori, Paul Y.; Hird, Trevor J.; Fraenkel, Monica C.; Wilcox, Pearce; Davidson, A. G. F.; Speert, David P.

doi:10.1164/rccm.201002-0203oc

Cited by 72 publications

(88 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical data for all patients in this study were previously collected, as approved by the UBC Research Ethics Boards (H07-01396) (Zlosnik et al 2011). …”

Section: Clinical Isolate Collectionmentioning

confidence: 99%

See 1 more Smart Citation

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

et al. 2017

View full text Add to dashboard Cite

Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures-including immune responses and therapeutic interventions-shape bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collected Burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2-20 yr and a broad range of epidemic lineages. Systematic phenotypic tests identified longitudinal bacterial series that manifested progressive changes in liquid media growth, motility, biofilm formation, and acute insect virulence, but not in mucoidy. The results suggest that distinct lineages follow distinct evolutionary trajectories during lung infection. Pan-genome analysis identified 10,110 homologous gene clusters present only in a subset of strains, including genes restricted to different molecular types. Our phylogenetic analysis based on 2148 orthologous gene clusters from all isolates is consistent with patient-specific clades. This suggests that initial colonization of patients was likely by individual strains, followed by subsequent diversification. Evidence of clonal lineages shared by some patients was observed, suggesting inter-patient transmission. We observed recurrent gene losses in multiple independent longitudinal series, including complete loss of Chromosome III and deletions on other chromosomes. Recurrently observed loss-of-function mutations were associated with decreases in motility and biofilm formation. Together, our study provides the first comprehensive genome-phenome analyses of B. cenocepacia infection in cystic fibrosis lungs and serves as a valuable resource for understanding the genomic and phenotypic underpinnings of bacterial evolution.

show abstract

“…Clinical data for all patients in this study were previously collected, as approved by the UBC Research Ethics Boards (H07-01396) (Zlosnik et al 2011). …”

Section: Clinical Isolate Collectionmentioning

confidence: 99%

“…Cold Spring Harbor Laboratory Press on May 10, 2018 -Published by genome.cshlp.org Downloaded from established protocol Zlosnik et al 2011Zlosnik et al , 2015.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Characteristic organisms associated with airway infection in patients with CF are, most notably, Staphylococcus aureus in the early course of the disease and P. aeruginosa at a later stage [26]. However, there is increasing appreciation that the lower airways of CF patients harbour communities of bacteria far more complex than previously thought and which include, amongst others, Stenotrophomonas maltophilia, isolates of the species Burkholderia cepacia, nontuberculous mycobacteria, fungi and viruses [27][28][29].…”

Section: Cystic Fibrosismentioning

confidence: 99%

Long-term macrolide treatment for chronic respiratory disease

2012

View full text Add to dashboard Cite

Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert antiinflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials. @ERSpublications Several studies evaluating macrolide antibiotics for the treatment of chronic respiratory diseases are underway

show abstract

“…Phenotypic changes in Bcc isolates during the course of infection have also been described. In contrast to P. aeruginosa, Bcc changes from a mucoid to a non-mucoid phenotype during chronic colonisation and patients which were infected exclusively with non-mucoid Bcc had a more rapid decline in lung function than those infected with mucoid bacteria [32 ]. Bcc mucoid isolates also lost expression of virulence factors and acquired a mutation in a quorum sensing (QS) gene during chronic infection [33].…”

Section: Adaptation Of Bacterial Pathogens To the Cf Lungmentioning

confidence: 99%

Bacterial host interactions in cystic fibrosis

Callaghan

McClean

2012

Current Opinion in Microbiology

View full text Add to dashboard Cite

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:http://www.elsevier.com/copyrightAuthor's personal copy Bacterial host interactions in cystic fibrosis Má ire Callaghan and Siobhá n McCleanChronic infection is a hallmark of cystic fibrosis (CF) and the main contributor to morbidity. Microbial infection in CF is complex, due to the number of different species that colonise the CF lung. Their colonisation is facilitated by a host response that is impaired or compromised by highly viscous mucous, zones of hypoxia and the lack of the cystic fibrosis transmembrane regulator (CFTR). Successful dominant CF pathogens combine an effective arsenal to establish infection and counter-attack the host response, together with an ability to adapt readily to an unfavourable environment. Hypermutability is common among CF pathogens facilitating adaptation and as the host response persists, progressive destruction of the normal architecture of lung tissue ensues with catastrophic consequences for the host. Limited information exists on the host-microbial interactions of many of these organisms and this review will focus only on the current understanding of the more clearly defined CF pathogens (Box 1). Role of CFTR in CF lung colonisationA direct role of the CFTR mutation in CF pathogenesis has been attributed to normal CFTR acting as a pathogen receptor involved in the internalisation and subsequent clearance of P. aeruginosa [9], but this mechanism is pathogen-specific. Mutated CFTR has also been attributed to be the cause of reduced internalisation of one Bcc species, Burkholderia dolosa, but not the more virulent Burkholderia cenocepacia in respiratory epithelial cells [10]. Furthermore, in contrast to P. aeruginosa, S. aureus was more invasive of CF cells compared to non-CF cells [11], indicating that CFTR is not the only route of bacterial uptake and invasion into the epithelium.Alterations in the phenotype of CF airway epithelial cells also provide receptors for pathogens to adhere to. For example, CF airways show alterations in membrane glycoproteins and glycolipids which are directly linked to the CFTR defect (reviewed by [12]). The ratio of asialylated to sialylated glycolipids is higher in CF cells compared to non-CF cells, providing additional receptors for P. aeruginosa and Bcc. This is significant as invasion of lung epithelial cells by Bcc depends on asialylated glycolipids [13]. In addition, alteration...

show abstract

Mucoid and Nonmucoid Burkholderia cepacia Complex Bacteria in Cystic Fibrosis Infections

Cited by 72 publications

References 30 publications

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

Long-term macrolide treatment for chronic respiratory disease

Bacterial host interactions in cystic fibrosis

Contact Info

Product

Resources

About