Variable virulence factors in Burkholderia pseudomallei (melioidosis) associated with human disease

PLoS One. 2014 Mar 11;9(3):e91682. doi: 10.1371/journal.pone.0091682. eCollection 2014.

Abstract

Burkholderia pseudomallei is a Gram-negative environmental bacterium that causes melioidosis, a potentially life-threatening infectious disease affecting mammals, including humans. Melioidosis symptoms are both protean and diverse, ranging from mild, localized skin infections to more severe and often fatal presentations including pneumonia, septic shock with multiple internal abscesses and occasionally neurological involvement. Several ubiquitous virulence determinants in B. pseudomallei have already been discovered. However, the molecular basis for differential pathogenesis has, until now, remained elusive. Using clinical data from 556 Australian melioidosis cases spanning more than 20 years, we identified a Burkholderia mallei-like actin polymerization bimA(Bm) gene that is strongly associated with neurological disease. We also report that a filamentous hemagglutinin gene, fhaB3, is associated with positive blood cultures but is negatively correlated with localized skin lesions without sepsis. We show, for the first time, that variably present virulence factors play an important role in the pathogenesis of melioidosis. Collectively, our study provides a framework for assessing other non-ubiquitous bacterial virulence factors and their association with disease, such as candidate loci identified from large-scale microbial genome-wide association studies.

MeSH terms

  • Australia
  • Burkholderia pseudomallei / genetics*
  • Burkholderia pseudomallei / pathogenicity*
  • Humans
  • Melioidosis / microbiology*
  • Microfilament Proteins / genetics
  • Virulence
  • Virulence Factors / genetics

Substances

  • BimA protein, Burkholderia pseudomallei
  • Microfilament Proteins
  • Virulence Factors

Grant support

This work was funded by the Australian National Health and Medical Research Council via project grant awards 605820 and 1046812. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.