<i>Burkholderia</i> Species Infections in Patients with Cystic Fibrosis in British Columbia, Canada. 30 Years’ Experience

Zlosnik, James E. A.; Zhou, Guohai; Brant, Rollin; Henry, Deborah A.; Hird, Trevor J.; Mahenthiralingam, Eshwar; Chilvers, Mark; Wilcox, Pearce; Speert, David P.

doi:10.1513/annalsats.201408-395oc

Cited by 95 publications

(103 citation statements)

References 46 publications

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“…1; Zlosnik et al 2015). Bcc isolates were typed by RAPD analyses, which used random primers to generate electrophoretic patterns that differ among divergent isolates (Mahenthiralingam et al 1996;Speert et al 2002a).…”

Section: A Longitudinal Collection Of B Cenocepacia Bacterial Isolatesmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: A Longitudinal Collection Of B Cenocepacia Bacterial Isolatesmentioning

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

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“…All Bcc members can trigger chronic airway infections in patients with CF and have emerged as opportunistic pulmonary pathogens (3). Burkholderia cenocepacia and B. multivorans are the two most commonly isolated species (4,5), which are threats for outbreaks. Bcc infections in patients with CF are associated with enhanced morbidity and mortality.…”

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Crystal structures of theBurkholderia multivoranshopanoid transporter HpnN

Kumar

Chou

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Strains of the Burkholderia cepacia complex (Bcc) are Gram-negative opportunisitic bacteria that are capable of causing serious diseases, mainly in immunocompromised individuals. Bcc pathogens are intrinsically resistant to multiple antibiotics, including β-lactams, aminoglycosides, fluoroquinolones, and polymyxins. They are major pathogens in patients with cystic fibrosis (CF) and can cause severe necrotizing pneumonia, which is often fatal. Hopanoid biosynthesis is one of the major mechanisms involved in multiple antimicrobial resistance of Bcc pathogens. The hpnN gene of B. multivorans encodes an integral membrane protein of the HpnN family of transporters, which is responsible for shuttling hopanoids to the outer membrane. Here, we report crystal structures of B. multivorans HpnN, revealing a dimeric molecule with an overall butterfly shape. Each subunit of the transporter contains 12 transmembrane helices and two periplasmic loops that suggest a plausible pathway for substrate transport. Further analyses indicate that HpnN is capable of shuttling hopanoid virulence factors from the outer leaflet of the inner membrane to the periplasm. Taken together, our data suggest that the HpnN transporter is critical for multidrug resistance and cell wall remodeling in Burkholderia.

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“…The declining prevalence of MRSA in this patient population is exceptional particularly when compared to CF Centres in the USA where there has been a progressive increase in its prevalence over the past 15 years (Cystic Fibrosis Foundation 2015). Consistent with our earlier work, we demonstrated that fewer patients acquired B. cepacia complex infection in the latter part of the study Zlosnik et al 2015), which may reflect stringent infection control 63 practices and the use of antibiotic therapy to attempt to eradicate Burkholderia (Chmiel et al 2014).Nevertheless, new cases of sporadic B. cepacia complex infection continue, emphasising the need for vigilant microbiological surveillance Zlosnik et al 2015).A key finding of our study is the observation of declining prevalence of P. aeruginosa and improving pulmonary function of the transitioning patients. It is likely that aggressive strategies aimed at early identification by increased culture sampling and eradication of P. aeruginosa infection are important components of the improvements in lung function observed here.…”

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confidence: 93%

Diversity of environmental and clinical Pseudomonas aeruginosa isolates

Ramsay¹

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Background and AimsThe bacterium Pseudomonas aeruginosa is a versatile environmental organism which is capable of persisting within a diverse range of habitats. For people with cystic fibrosis (CF), P. aeruginosa is the most common bacterial species isolated from respiratory secretions and infection is associated with poor health outcomes and decreased life expectancy.Molecular-based epidemiological studies have shown that patients with CF can harbour indistinguishable genotypes (shared strains) of P. aeruginosa that have not been isolated from natural or commonly encountered environments sources. It is speculated that these shared strains are acquired by person-to-person transmission and have become highly niche-adapted to the CF airway. However, the specific mechanisms relating to the transmission, host adaptation and persistence of these strains remain uncertain.By thoroughly characterising P. aeruginosa isolates from a defined cohort of patients this thesis aims to determine the prevalence and diversity of strains among adults with CF, and using phenotypic and genomic methods, to explore the key differences pertaining to adaptation between shared and unique strains of P. aeruginosa strains sourced from a range of ecological settings. MethodsLongitudinal analysis of respiratory pathogens from adults with CF was undertaken to determine the prevalence of P. aeruginosa and other major CF pathogens. Univariate analysis was conducted to determine change in prevalence over time.P. aeruginosa isolates at two time points from adults with CF underwent single nucleotide polymorphism (SNP) based genotyping to assess the incidence and prevalence of shared strains. Statistical analyses was undertaken to find associations between acquisition of shared strains and health outcomes.Bacterial motility and adhesion was determined for clinical (CF, non-CF and animal) and environmental P. aeruginosa isolates. Each assay was performed under varied atmospheric conditions. Regression analysis was performed to assess an association between genotype and phenotype.iii CF and environmental P. aeruginosa isolates were grown a dynamic flow cell system to allow for the development and visualisation of biofilm structures. Following incubation and staining, three dimensional images were captured and resulting data analysed using Comstat software.Mixed effects models were used to compare relevant biofilm parameters.Bioinformatic analysis was performed on CF and environmental P. aeruginosa isolates.Genetic variants associated with phenotypic characteristics were identified. ResultsThe prevalence of significant airway pathogens declined over the study period. For paediatric patients at the time of transition, this decline was correlated with an improvement in lung function. Interestingly, the prevalence of chronic P. aeruginosa infection remained stable.While the proportion of patients harbouring the shared strain AUST-02 declined over time, there was a marked increase in those infected with the AUST-06 strain. In contrast, the prevale...

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Burkholderia Species Infections in Patients with Cystic Fibrosis in British Columbia, Canada. 30 Years’ Experience

Cited by 95 publications

References 46 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

Crystal structures of theBurkholderia multivoranshopanoid transporter HpnN

Diversity of environmental and clinical Pseudomonas aeruginosa isolates

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