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Genomic Expression Analysis Reveals Strategies of Burkholderia cenocepacia to Adapt to Cystic Fibrosis Patients' Airways and Antimicrobial Therapy

By Nuno P. Mira, Andreia Madeira, Ana Sílvia Moreira, Carla P. Coutinho and Isabel Sá-Correia

Abstract

Pulmonary colonization of cystic fibrosis (CF) patients with Burkholderia cenocepacia or other bacteria of the Burkholderia cepacia complex (Bcc) is associated with worse prognosis and increased risk of death. During colonization, the bacteria may evolve under the stressing selection pressures exerted in the CF lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. Understanding the adaptive mechanisms that promote successful colonization and long-term survival of B. cenocepacia in the CF lung is essential for an improved therapeutic outcome of chronic infections. To get mechanistic insights into these adaptive strategies a transcriptomic analysis, based on DNA microarrays, was explored in this study. The genomic expression levels in two clonal variants isolated during long-term colonization of a CF patient who died from the cepacia syndrome were compared. One of the isolates examined, IST439, is the first B. cenocepacia isolate retrieved from the patient and the other isolate, IST4113, was obtained three years later and is more resistant to different classes of antimicrobials. Approximately 1000 genes were found to be differently expressed in the two clonal variants reflecting a marked reprogramming of genomic expression. The up-regulated genes in IST4113 include those involved in translation, iron uptake (in particular, in ornibactin biosynthesis), efflux of drugs and in adhesion to epithelial lung tissue and to mucin. Alterations related with adaptation to the nutritional environment of the CF lung and to an oxygen-limited environment are also suggested to be a key feature of transcriptional reprogramming occurring during long-term colonization, antibiotic therapy and the progression of the disease

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3244429
Provided by: PubMed Central

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Citations

  1. (2010). A decade of Burkholderia cenocepacia virulence determinant research.
  2. (1999). A novel mucin-sulphatase activity found in Burkholderia cepacia and Pseudomonas aeruginosa.
  3. (2010). A TNF-like trimeric lectin domain from Burkholderia cenocepacia with specificity for fucosylated human histo-blood group antigens.
  4. (2005). Altered Oglycosylation and sulfation of airway mucins associated with cystic fibrosis.
  5. (2006). An instrument-free method for the demonstration of efflux pump activity of bacteria.
  6. (2007). Antibiotic resistance of Burkholderia spp. In:
  7. (2007). Architecture of Burkholderia cepacia complex sigma70 gene family: evidence of alternative primary and clade-specific factors, and genomic instability.
  8. (2004). Arginine and Polyamine Metabolism. In:
  9. (2009). Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance.
  10. (2011). Burkholderia cenocepacia clonal phenotypic variation during three and a half years of residence in the lungs of a cystic fibrosis patient.
  11. (2010). Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence.
  12. (2009). Burkholderia cenocepacia O antigen lipopolysaccharide prevents phagocytosis by macrophages and adhesion to epithelial cells.
  13. (2006). Burkholderia cenocepacia utilizes ferritin as an iron source.
  14. (2005). Cable pili and the 22-kilodalton adhesin are required for Burkholderia cenocepacia binding to and transmigration across the squamous epithelium.
  15. (2005). Characterization of the cciIR quorum-sensing system in Burkholderia cenocepacia.
  16. (2000). Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa.
  17. (2003). Contribution of the MexXY multidrug transporter to aminoglycoside resistance in Pseudomonas aeruginosa clinical isolates.
  18. (2011). Cooperation between LepA and PlcH contributes to the in vivo virulence and growth of Pseudomonas aeruginosa in mice.
  19. (2005). Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology.
  20. (2011). Deciphering the role of RND efflux transporters in Burkholderia cenocepacia.
  21. (2011). Differential adaptation of microbial pathogens to airways of patients with cystic fibrosis and chronic obstructive pulmonary disease.
  22. (2009). Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis.
  23. (2006). Efflux pump genes of the resistance-nodulation-division family in Burkholderia cenocepacia genome.
  24. (2008). Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection.
  25. (2011). Evolutionary dynamics of bacteria in a human host environment.
  26. (2007). Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection.
  27. (2007). Exceptionally high representation of Burkholderia cepacia among B. cepacia complex isolates recovered from the Major Portuguese Cystic Fibrosis Center.
  28. (2004). Expression of acrB, acrF, acrD, marA,a n d soxS in Salmonella enterica serovar Typhimurium: role in multiple antibiotic resistance.
  29. (2008). Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum.
  30. (2006). Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients.
  31. (2010). Genome-wide analysis of DNA repeats in Burkholderia cenocepacia J2315 identifies a novel adhesin-like gene unique to epidemic-associated strains of the ET-12 lineage.
  32. (2000). High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection.
  33. Hoang TT (2007) In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients.
  34. (2004). Importance of the ornibactin and pyochelin siderophore transport systems in Burkholderia cenocepacia lung infections.
  35. (2000). Increased sputum amino acid concentrations and auxotrophy of Pseudomonas aeruginosa in severe cystic fibrosis lung disease.
  36. (2005). Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction.
  37. (2010). Influence of RpoN on isocitrate lyase activity in Pseudomonas aeruginosa.
  38. (2009). Interactions of Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria with epithelial and phagocytic cells.
  39. (1986). Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance.
  40. (2000). Iron metabolism in pathogenic bacteria.
  41. (2002). Life and death in a macrophage: role of the glyoxylate cycle in virulence.
  42. (1984). Lipopolysaccharide changes in impermeability-type aminoglycoside resistance in Pseudomonas aeruginosa.
  43. (1999). Lipopolysaccharide chemotypes of Burkholderia cepacia.
  44. (2010). Metabolic network analysis of Pseudomonas aeruginosa during chronic cystic fibrosis lung infection.
  45. (2007). Microbial ecology of the cystic fibrosis lung.
  46. (2003). Molecular Analysis of Burkholderia cepacia Complex Isolates from a Portuguese Cystic Fibrosis Center: a 7-Year Study.
  47. (2007). Molecular epidemiology and dynamics of Pseudomonas aeruginosa populations in lungs of cystic fibrosis patients.
  48. (2011). Molecular mechanisms of chlorhexidine tolerance in Burkholderia cenocepacia biofilms.
  49. (2005). Multilocus sequence typing scheme that provides both species and strain differentiation for the Burkholderia cepacia complex.
  50. (2010). Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway.
  51. (2007). Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum.
  52. (1988). Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates.
  53. (2009). Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence.
  54. (2011). Quantitative proteomics (2-D DIGE) reveals molecular strategies employed by Burkholderia cenocepacia to adapt to the airways of cystic fibrosis patients under antimicrobial therapy.
  55. (2009). Reciprocal regulation by the CepIR and CciIR quorum sensing systems in Burkholderia cenocepacia.
  56. (2007). Responses of Pseudomonas aeruginosa to low oxygen indicate that growth in the cystic fibrosis lung is by aerobic respiration.
  57. (2008). Revisiting the host as a growth medium.
  58. (2000). Riding the sulfur cycle-metabolism of sulfonates and sulfate esters in gram-negative bacteria.
  59. (2002). Role of flagella in host cell invasion by Burkholderia cepacia.
  60. (1982). Role of porin proteins OmpF and OmpC in the permeation of beta-lactams.
  61. (2008). Structural basis for mannose recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia.
  62. (2010). Structural basis of the affinity for oligomannosides and analogs displayed by BC2L-A, a Burkholderia cenocepacia soluble lectin.
  63. (1994). Taurine modulation of hypochlorous acid-induced lung epithelial cell injury in vitro. Role of anion transport.
  64. (2011). The Burkholderia cenocepacia LysR-type transcriptional regulator ShvR influences B. cenocepacia Transcriptome Variation
  65. (2004). The Burkholderia cepacia epidemic strain marker is part of a novel genomic island encoding both virulence and metabolism-associated genes in Burkholderia cenocepacia.
  66. (1997). The cioAB genes from Pseudomonas aeruginosa code for a novel cyanide-insensitive terminal oxidase related to the cytochrome bd quinol oxidases.
  67. (2009). The genome of Burkholderia cenocepacia J2315, an epidemic pathogen of cystic fibrosis patients.
  68. (1996). The high amino-acid content of sputum from cystic fibrosis patients promotes growth of auxotrophic Pseudomonas aeruginosa.JM e d
  69. (2005). The multifarious, multireplicon Burkholderia cepacia complex.
  70. (2006). The ornibactin biosynthesis and transport genes of Burkholderia cenocepacia are regulated by an extracytoplasmic function sigma factor which is a part of the Fur regulon.
  71. (2004). The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase.
  72. (2005). Use of suppression-subtractive hybridization to identify genes in the Burkholderia cepacia complex that are unique to Burkholderia cenocepacia.
  73. (2008). Variation of the antimicrobial susceptibility profiles of Burkholderia cepacia complex clonal isolates obtained from chronically infected cystic fibrosis patients: a five-year survey in the major Portuguese treatment center.
  74. (2008). Virulence determinants from a cystic fibrosis isolate of Pseudomonas aeruginosa include isocitrate lyase.
  75. (2003). Wholegenome sequence variation among multiple isolates of Pseudomonas aeruginosa.

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