Genetic similarity of Burkholderia cenocepacia from cystic fibrosis patients

Pretto, Luana; de‐Paris, Fernanda; Machado, Alice Beatriz Mombach Pinheiro; Martins, Andreza Francisco; Barth, Afonso Luís

doi:10.1016/j.bjid.2012.09.002

Cited by 3 publications

(2 citation statements)

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“…CF patients infected with genotypically similar Burkholderia strains can have drastically different clinical outcomes. While useful for tracking Bcc epidemics, current genotyping methods-such as pulse-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and PCR-based methods with randomly amplified polymorphic DNA (RAPD) or BOX-PCR (Govan et al 1993;Jones et al 2004) -are not sufficient to define the scope of genetic diversity in infectious B. cenocepacia strains or to identify the underlying genetic differences responsible for variation in bacterial phenotypes that influence clinical outcomes (Mahenthiralingam et al 2000;Speert et al 2002a;Vonberg et al 2006;Pretto et al 2013). These low-resolution genotyping methods have shown that long-term sequential isolates from one patient typically belong to the same clonal type but nevertheless show phenotypic diversity (Cunha et al 2003;Coutinho et al 2011a,b).…”

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

et al. 2017

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“…By using recA gene sequence analysis and multilocus sequence typing, B. cenocepacia may be subdivided into four phylogenetic clusters, IIIA to IIID [7]. However, almost all clinically relevant isolates belong to the IIIA and IIIB groups [8, 9]. Epidemiological studies showed that strains ET-12 and several other epidemic dominant in Canada and Europe are part of the IIIA subgroup [10].…”

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Identification and analysis of genomic islands in Burkholderia cenocepacia AU 1054 with emphasis on pathogenicity islands

et al. 2017

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BackgroundGenomic islands (GIs) are genomic regions that reveal evidence of horizontal DNA transfer. They can code for many functions and may augment a bacterium’s adaptation to its host or environment. GIs have been identified in strain J2315 of Burkholderia cenocepacia, whereas in strain AU 1054 there has been no published works on such regions according to our text mining and keyword search in Medline.ResultsIn this study, we identified 21 GIs in AU 1054 by combining two computational tools. Feature analyses suggested that the predictions are highly reliable and hence illustrated the advantage of joint predictions by two independent methods. Based on putative virulence factors, four GIs were further identified as pathogenicity islands (PAIs). Through experiments of gene deletion mutants in live bacteria, two putative PAIs were confirmed, and the virulence factors involved were identified as lipA and copR. The importance of the genes lipA (from PAI 1) and copR (from PAI 2) for bacterial invasion and replication indicates that they are required for the invasive properties of B. cenocepacia and may function as virulence determinants for bacterial pathogenesis and host infection.ConclusionsThis approach of in silico prediction of GIs and subsequent identification of potential virulence factors in the putative island regions with final validation using wet experiments could be used as an effective strategy to rapidly discover novel virulence factors in other bacterial species and strains.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-0986-6) contains supplementary material, which is available to authorized users.

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Insights into the genome diversity and virulence of two clinical isolates of Burkholderia cenocepacia

Salloum

Nassour

Araj

et al. 2018

Journal of Medical Microbiology

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Genetic similarity of Burkholderia cenocepacia from cystic fibrosis patients

Cited by 3 publications

References 16 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

Identification and analysis of genomic islands in Burkholderia cenocepacia AU 1054 with emphasis on pathogenicity islands

Insights into the genome diversity and virulence of two clinical isolates of Burkholderia cenocepacia

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