title: Variable virulence factors in Burkholderia pseudomallei (melioidosis) associated with human disease.
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.
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Sarovich
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Erin P
authors.initials: EP
authors.lastname: Price
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Webb
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Ward
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Marcos Y
authors.initials: MY
authors.lastname: Voutsinos
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawai'i, Honolulu, Hawai'i, United States of America.
authors.forename: Apichai
authors.initials: A
authors.lastname: Tuanyok
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Mayo
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kaestli
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Infectious Diseases Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Currie
mesh_terms: D001315:Australia; D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D008554:Melioidosis / Q000382:microbiology*; D008840:Microfilament Proteins / Q000235:genetics; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: C503173:BimA protein, Burkholderia pseudomallei; D008840:Microfilament Proteins; D037521:Virulence Factors