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PMID: 16997946 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Global map of growth-regulated gene expression in Burkholderia pseudomallei, the causative agent of melioidosis.

Journal of bacteriology ·Vol. 188 ·No. 23 ·2006-12-00 ·Pages 8178-88

Rodrigues F, Sarkar-Tyson M, Harding SV, Sim SH, Chua HH, Lin CH, Han X, Karuturi RK, Sung K, Yu K, Chen W, Atkins TP, Titball RW, Tan P

Abstract

Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial growth to pathogenicity, we have characterized the growth transcriptome of Burkholderia pseudomallei, the causative agent of melioidosis. Using a fine-scale sampling approach, we found approximately 17% of all B. pseudomallei genes displaying regulated expression during growth in rich medium, occurring as broad waves of functionally coherent gene expression tightly associated with distinct growth phases and transition points. We observed regulation of virulence genes across all growth phases and identified serC as a potentially new virulence factor by virtue of its coexpression with other early-phase virulence genes. serC-disrupted B. pseudomallei strains were serine auxotrophs and in mouse infection assays exhibited a dramatic attenuation of virulence compared to wild-type B. pseudomallei. Immunization of mice with serC-disrupted B. pseudomallei also conferred protection against subsequent challenges with different wild-type B. pseudomallei strains. At a genomic level, early-phase genes were preferentially localized on chromosome 1, while stationary-phase genes were significantly biased towards chromosome 2. We detected a significant level of chromosomally clustered gene expression, allowing us to predict approximately 100 potential operons in the B. pseudomallei genome. We computationally and experimentally validated these operons by showing that genes in these regions are preferentially transcribed in the same 5'-->3' direction, possess significantly shorter intergenic lengths than the overall genome, and are expressed as a common mRNA transcript. The availability of this transcriptome map provides an important resource for understanding the transcriptional architecture of B. pseudomallei.

MeSH Terms
Animals Bacterial Vaccines/administration & dosage Burkholderia pseudomallei/genetics,growth & development,immunology,pathogenicity Chromosomes, Bacterial/genetics Female Gene Deletion Gene Expression Profiling Gene Expression Regulation, Bacterial Genes, Bacterial Genome, Bacterial Melioidosis/microbiology,prevention & control Mice Mice, Inbred BALB C Multigene Family Oligonucleotide Array Sequence Analysis Vaccination Virulence Virulence Factors/genetics
Chemicals
Bacterial Vaccines Virulence Factors
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Rodrigues Fiona
Genome Institute of Singapore, 60 Biopolis Street, no. 02-01, Genome, Singapore 138672, Republic of Singapore.
Sarkar-Tyson Mitali
Harding Sarah V
Sim Siew Hoon
Chua Hui Hoon
Lin Chi Ho
Han Xu
Karuturi R Krishna M
Sung Ken
Yu Kun
Chen Wei
Atkins Timothy P
Titball Richard W
Tan Patrick
References (46)
46 references, click to expand
  1. Gene expression profiling of Helicobacter pylori reveals a growth-phase-dependent switch in virulence gene expression.
    Infect Immun. 2003 May;71(5):2643-55 PMID: 12704139
  2. The production of an auxotrophic marked, plasmid-cured Salmonella ser. Typhimurium as a live attenuated vaccine.
    Onderstepoort J Vet Res. 1998 Sep;65(3):213-20 PMID: 9809326
  3. 3-hydroxypyruvate substitutes for pyridoxine in serC mutants of Escherichia coli K-12.
    J Bacteriol. 1978 Jun;134(3):944-9 PMID: 350858
  4. The estimation of the bactericidal power of the blood.
    J Hyg (Lond). 1938 Nov;38(6):732-49 PMID: 20475467
  5. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  6. Genetic evidence that Legionella pneumophila RpoS modulates expression of the transmission phenotype in both the exponential phase and the stationary phase.
    Infect Immun. 2004 May;72(5):2468-76 PMID: 15102753
  7. Melioidosis: epidemiology, pathophysiology, and management.
    Clin Microbiol Rev. 2005 Apr;18(2):383-416 PMID: 15831829
  8. Growth phase-regulated induction of Salmonella-induced macrophage apoptosis correlates with transient expression of SPI-1 genes.
    J Bacteriol. 1999 Jun;181(11):3433-7 PMID: 10348855
  9. ppGpp-dependent stationary phase induction of genes on Salmonella pathogenicity island 1.
    J Biol Chem. 2004 Aug 13;279(33):34183-90 PMID: 15161921
  10. Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays.
    Genes Dev. 2001 Dec 1;15(23):3183-92 PMID: 11731481
  11. Global stage-specific gene regulation during the developmental cycle of Chlamydia trachomatis.
    J Bacteriol. 2003 May;185(10):3179-89 PMID: 12730178
  12. A mutant of Burkholderia pseudomallei, auxotrophic in the branched chain amino acid biosynthetic pathway, is attenuated and protective in a murine model of melioidosis.
    Infect Immun. 2002 Sep;70(9):5290-4 PMID: 12183585
  13. A cysteine/methionine auxotroph of the opportunistic fungus Aspergillus flavus is associated with host-range restriction: a model for emerging diseases.
    Microbiology. 2006 Jan;152(Pt 1):223-32 PMID: 16385132
  14. Integrative genomic, transcriptional, and proteomic diversity in natural isolates of the human pathogen Burkholderia pseudomallei.
    J Bacteriol. 2005 Jun;187(12):4276-85 PMID: 15937190
  15. Serum amino acid concentrations in nine athletes before and after the 1993 Colmar ultra triathlon.
    Int J Sports Med. 1995 Apr;16(3):155-9 PMID: 7649705
  16. Isolation and characterization of arginine auxotrophs of Cryptococcus neoformans.
    Infect Immun. 1980 Mar;27(3):910-4 PMID: 6991434
  17. Transcriptome analysis of Escherichia coli using high-density oligonucleotide probe arrays.
    Nucleic Acids Res. 2002 Sep 1;30(17):3732-8 PMID: 12202758
  18. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment.
    J Bacteriol. 2003 Apr;185(7):2080-95 PMID: 12644477
  19. Transcriptome of uropathogenic Escherichia coli during urinary tract infection.
    Infect Immun. 2004 Nov;72(11):6373-81 PMID: 15501767
  20. The BpsIR quorum-sensing system of Burkholderia pseudomallei.
    J Bacteriol. 2005 Jan;187(2):785-90 PMID: 15629951
  21. Formation and composition of the Bacillus anthracis endospore.
    J Bacteriol. 2004 Jan;186(1):164-78 PMID: 14679236
  22. Identification of cell cycle-regulated genes in fission yeast.
    Mol Biol Cell. 2005 Mar;16(3):1026-42 PMID: 15616197
  23. Melioidosis, northeastern Brazil.
    Emerg Infect Dis. 2005 Sep;11(9):1458-60 PMID: 16229782
  24. Detection of bacterial virulence genes by subtractive hybridization: identification of capsular polysaccharide of Burkholderia pseudomallei as a major virulence determinant.
    Infect Immun. 2001 Jan;69(1):34-44 PMID: 11119486
  25. Patterns of large-scale genomic variation in virulent and avirulent Burkholderia species.
    Genome Res. 2004 Nov;14(11):2295-307 PMID: 15520292
  26. The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence.
    Mol Microbiol. 1998 Dec;30(5):1081-100 PMID: 9988483
  27. Serum amino acid concentrations in aging men and women.
    Amino Acids. 2003 Jun;24(4):413-21 PMID: 12768504
  28. Global analysis of the genetic network controlling a bacterial cell cycle.
    Science. 2000 Dec 15;290(5499):2144-8 PMID: 11118148
  29. Characterization of auxotrophic mutants of Mycobacterium tuberculosis and their potential as vaccine candidates.
    Infect Immun. 2001 Feb;69(2):1142-50 PMID: 11160012
  30. Operon prediction by comparative genomics: an application to the Synechococcus sp. WH8102 genome.
    Nucleic Acids Res. 2004;32(7):2147-57 PMID: 15096577
  31. Genes aroA and serC of Salmonella typhimurium constitute an operon.
    J Bacteriol. 1985 Jul;163(1):355-61 PMID: 2989248
  32. A powerful non-homology method for the prediction of operons in prokaryotes.
    Bioinformatics. 2002;18 Suppl 1:S329-36 PMID: 12169563
  33. Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei.
    Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14240-5 PMID: 15377794
  34. Lipopolysaccharide from nonvirulent Ara+ Burkholderia pseudomallei isolates is immunologically indistinguishable from lipopolysaccharide from virulent Ara- clinical isolates.
    Clin Diagn Lab Immunol. 1998 Mar;5(2):225-9 PMID: 9521147
  35. Co-expression pattern from DNA microarray experiments as a tool for operon prediction.
    Nucleic Acids Res. 2002 Jul 1;30(13):2886-93 PMID: 12087173
  36. Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei.
    J Med Microbiol. 2004 Nov;53(Pt 11):1053-64 PMID: 15496380
  37. A novel method for accurate operon predictions in all sequenced prokaryotes.
    Nucleic Acids Res. 2005;33(3):880-92 PMID: 15701760
  38. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity.
    J Bacteriol. 2003 Aug;185(16):4992-6 PMID: 12897019
  39. Construction of delta aroA his delta pur strains of Salmonella typhi.
    J Bacteriol. 1988 Sep;170(9):3991-5 PMID: 2842296
  40. Flagella are virulence determinants of Burkholderia pseudomallei.
    Infect Immun. 2003 Apr;71(4):1622-9 PMID: 12654773
  41. Missing value estimation methods for DNA microarrays.
    Bioinformatics. 2001 Jun;17(6):520-5 PMID: 11395428
  42. Intracytoplasmic growth and virulence of Listeria monocytogenes auxotrophic mutants.
    Infect Immun. 1993 Sep;61(9):3756-60 PMID: 8359896
  43. The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.
    PLoS Biol. 2003 Oct;1(1):E5 PMID: 12929205
  44. The Burkholderia pseudomallei RpoE (AlgU) operon is involved in environmental stress tolerance and biofilm formation.
    FEMS Microbiol Lett. 2005 Nov 15;252(2):243-9 PMID: 16185818
  45. Growth phase-dependent invasion of Pseudomonas aeruginosa and its survival within HeLa cells.
    Infect Immun. 2001 Jul;69(7):4398-406 PMID: 11401979
  46. Melioidosis: an emerging infection in Taiwan?
    Emerg Infect Dis. 2001 May-Jun;7(3):428-33 PMID: 11384520
Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
Published
2006-12-00
Epub
2006-00-22
Pages
8178-88
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC1698202
Subset
IM
Databases
GEO
Analysis Services
Analysis Services

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