Burkholderia pseudomallei lipopolysaccharide genotype does not correlate with severity or outcome in melioidosis

host risk factors remain the critical determinant

Jessica R. Webb, Derek S. Sarovich, Erin P. Price, Linda M. Ward, Mark Mayo, Bart J. Currie

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: The causative agent of melioidosis is the Gram-negative bacterium Burkholderia pseudomallei. Clinical presentations of melioidosis are notably diverse, with host risk factors considered central to progression from infection to disease and clinical outcome. Ubiquitous and variably present virulence determinants have been described for B. pseudomallei, with several variably present minority genotypes associated with specific disease presentations. The lipopolysaccharide (LPS) O-antigen of B. pseudomallei is highly diverse with four types described. Invitro data suggest differential virulence between LPS types but it remains unclear whether this LPS O-antigen diversity influences clinical presentation, severity and outcomes in patients with melioidosis.

    Methods: Whole-genome sequencing was performed to assign an LPS type to 1005 consecutive B. pseudomallei strains, each corresponding to a melioidosis patient enrolled in the 28 year Darwin Prospective Melioidosis study. Correlations of LPS genotype with clinical parameters was then undertaken.

    Results: Bivariate analysis demonstrated that mortality and the rates of bacteremia and septic shock were the same for patients with the two predominant B. pseudomallei LPS genotypes A (87% of cases) and B (12% of all cases). Mortality was 12% and 12%, bacteremia 57% and 53% and septic shock 22% and 18% for LPS A and LPS B, respectively.

    Conclusions: LPS genotype was not associated with melioidosis severity or outcome. These findings suggest that in vitro differential virulence between B. pseudomallei LPS genotypes does not translate to clinical significance and this supports the primary role of host risk factors in determining disease severity and outcomes in melioidosis.
    Original languageEnglish
    Article numberofz091
    Pages (from-to)1-5
    Number of pages5
    JournalOpen Forum Infectious Diseases
    Volume6
    Issue number4
    Early online date25 Feb 2019
    DOIs
    Publication statusPublished - Apr 2019

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    Melioidosis
    Burkholderia pseudomallei
    Lipopolysaccharides
    Genotype
    Virulence
    O Antigens
    Septic Shock
    Bacteremia
    Mortality
    Gram-Negative Bacteria
    Genome
    Prospective Studies

    Cite this

    @article{4abd3f23020c45f69c7530b6f0a8e0d4,
    title = "Burkholderia pseudomallei lipopolysaccharide genotype does not correlate with severity or outcome in melioidosis: host risk factors remain the critical determinant",
    abstract = "Background: The causative agent of melioidosis is the Gram-negative bacterium Burkholderia pseudomallei. Clinical presentations of melioidosis are notably diverse, with host risk factors considered central to progression from infection to disease and clinical outcome. Ubiquitous and variably present virulence determinants have been described for B. pseudomallei, with several variably present minority genotypes associated with specific disease presentations. The lipopolysaccharide (LPS) O-antigen of B. pseudomallei is highly diverse with four types described. Invitro data suggest differential virulence between LPS types but it remains unclear whether this LPS O-antigen diversity influences clinical presentation, severity and outcomes in patients with melioidosis.Methods: Whole-genome sequencing was performed to assign an LPS type to 1005 consecutive B. pseudomallei strains, each corresponding to a melioidosis patient enrolled in the 28 year Darwin Prospective Melioidosis study. Correlations of LPS genotype with clinical parameters was then undertaken.Results: Bivariate analysis demonstrated that mortality and the rates of bacteremia and septic shock were the same for patients with the two predominant B. pseudomallei LPS genotypes A (87{\%} of cases) and B (12{\%} of all cases). Mortality was 12{\%} and 12{\%}, bacteremia 57{\%} and 53{\%} and septic shock 22{\%} and 18{\%} for LPS A and LPS B, respectively.Conclusions: LPS genotype was not associated with melioidosis severity or outcome. These findings suggest that in vitro differential virulence between B. pseudomallei LPS genotypes does not translate to clinical significance and this supports the primary role of host risk factors in determining disease severity and outcomes in melioidosis.",
    keywords = "LPS O-antigen diversity, melioidosis, virulence",
    author = "Webb, {Jessica R.} and Sarovich, {Derek S.} and Price, {Erin P.} and Ward, {Linda M.} and Mark Mayo and Currie, {Bart J.}",
    year = "2019",
    month = "4",
    doi = "10.1093/ofid/ofz091",
    language = "English",
    volume = "6",
    pages = "1--5",
    journal = "Open Forum Infectious Diseases",
    issn = "2328-8957",
    publisher = "Oxford University Press",
    number = "4",

    }

    Burkholderia pseudomallei lipopolysaccharide genotype does not correlate with severity or outcome in melioidosis : host risk factors remain the critical determinant. / Webb, Jessica R.; Sarovich, Derek S.; Price, Erin P.; Ward, Linda M.; Mayo, Mark; Currie, Bart J.

    In: Open Forum Infectious Diseases, Vol. 6, No. 4, ofz091, 04.2019, p. 1-5.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Burkholderia pseudomallei lipopolysaccharide genotype does not correlate with severity or outcome in melioidosis

    T2 - host risk factors remain the critical determinant

    AU - Webb, Jessica R.

    AU - Sarovich, Derek S.

    AU - Price, Erin P.

    AU - Ward, Linda M.

    AU - Mayo, Mark

    AU - Currie, Bart J.

    PY - 2019/4

    Y1 - 2019/4

    N2 - Background: The causative agent of melioidosis is the Gram-negative bacterium Burkholderia pseudomallei. Clinical presentations of melioidosis are notably diverse, with host risk factors considered central to progression from infection to disease and clinical outcome. Ubiquitous and variably present virulence determinants have been described for B. pseudomallei, with several variably present minority genotypes associated with specific disease presentations. The lipopolysaccharide (LPS) O-antigen of B. pseudomallei is highly diverse with four types described. Invitro data suggest differential virulence between LPS types but it remains unclear whether this LPS O-antigen diversity influences clinical presentation, severity and outcomes in patients with melioidosis.Methods: Whole-genome sequencing was performed to assign an LPS type to 1005 consecutive B. pseudomallei strains, each corresponding to a melioidosis patient enrolled in the 28 year Darwin Prospective Melioidosis study. Correlations of LPS genotype with clinical parameters was then undertaken.Results: Bivariate analysis demonstrated that mortality and the rates of bacteremia and septic shock were the same for patients with the two predominant B. pseudomallei LPS genotypes A (87% of cases) and B (12% of all cases). Mortality was 12% and 12%, bacteremia 57% and 53% and septic shock 22% and 18% for LPS A and LPS B, respectively.Conclusions: LPS genotype was not associated with melioidosis severity or outcome. These findings suggest that in vitro differential virulence between B. pseudomallei LPS genotypes does not translate to clinical significance and this supports the primary role of host risk factors in determining disease severity and outcomes in melioidosis.

    AB - Background: The causative agent of melioidosis is the Gram-negative bacterium Burkholderia pseudomallei. Clinical presentations of melioidosis are notably diverse, with host risk factors considered central to progression from infection to disease and clinical outcome. Ubiquitous and variably present virulence determinants have been described for B. pseudomallei, with several variably present minority genotypes associated with specific disease presentations. The lipopolysaccharide (LPS) O-antigen of B. pseudomallei is highly diverse with four types described. Invitro data suggest differential virulence between LPS types but it remains unclear whether this LPS O-antigen diversity influences clinical presentation, severity and outcomes in patients with melioidosis.Methods: Whole-genome sequencing was performed to assign an LPS type to 1005 consecutive B. pseudomallei strains, each corresponding to a melioidosis patient enrolled in the 28 year Darwin Prospective Melioidosis study. Correlations of LPS genotype with clinical parameters was then undertaken.Results: Bivariate analysis demonstrated that mortality and the rates of bacteremia and septic shock were the same for patients with the two predominant B. pseudomallei LPS genotypes A (87% of cases) and B (12% of all cases). Mortality was 12% and 12%, bacteremia 57% and 53% and septic shock 22% and 18% for LPS A and LPS B, respectively.Conclusions: LPS genotype was not associated with melioidosis severity or outcome. These findings suggest that in vitro differential virulence between B. pseudomallei LPS genotypes does not translate to clinical significance and this supports the primary role of host risk factors in determining disease severity and outcomes in melioidosis.

    KW - LPS O-antigen diversity

    KW - melioidosis

    KW - virulence

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    DO - 10.1093/ofid/ofz091

    M3 - Article

    VL - 6

    SP - 1

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    JO - Open Forum Infectious Diseases

    JF - Open Forum Infectious Diseases

    SN - 2328-8957

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