Burkholderia pseudomallei Lipopolysaccharide Genotype Does Not Correlate With Severity or Outcome in Melioidosis: Host Risk Factors Remain the Critical Determinant.

Abstract

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 3 types described. In vitro 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. 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. Bivariate analysis demonstrated that mortality and the rates of bacteremia and septic shock were the same for patients with the 2 predominant B pseudomallei LPS genotypes A (87% of cases) and B (12% of all cases). Mortality was 12% and 12%, bacteremia was 57% and 53%, and septic shock was 22% and 18% for LPS A and LPS B, respectively. Lipopolysaccharide 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.