title: Tracing melioidosis back to the source: using whole-genome sequencing to investigate an outbreak originating from a contaminated domestic water supply.
abstract: Melioidosis, a disease of public health importance in Southeast Asia and northern Australia, is caused by the Gram-negative soil bacillus Burkholderia pseudomallei. Melioidosis is typically acquired through environmental exposure, and case clusters are rare, even in regions where the disease is endemic. B. pseudomallei is classed as a tier 1 select agent by the Centers for Disease Control and Prevention; from a biodefense perspective, source attribution is vital in an outbreak scenario to rule out a deliberate release. Two cases of melioidosis within a 3-month period at a residence in rural northern Australia prompted an investigation to determine the source of exposure. B. pseudomallei isolates from the property's groundwater supply matched the multilocus sequence type of the clinical isolates. Whole-genome sequencing confirmed the water supply as the probable source of infection in both cases, with the clinical isolates differing from the likely infecting environmental strain by just one single nucleotide polymorphism (SNP) each. For the first time, we report a phylogenetic analysis of genomewide insertion/deletion (indel) data, an approach conventionally viewed as problematic due to high mutation rates and homoplasy. Our whole-genome indel analysis was concordant with the SNP phylogeny, and these two combined data sets provided greater resolution and a better fit with our epidemiological chronology of events. Collectively, this investigation represents a highly accurate account of source attribution in a melioidosis outbreak and gives further insight into a frequently overlooked reservoir of B. pseudomallei. Our methods and findings have important implications for outbreak source tracing of this bacterium and other highly recombinogenic pathogens.
authors: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
authors: Evan
authors: E
authors: McRobb
authors: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
authors: Derek S
authors: http://orcid.org/0000-0002-6944-3980
authors: DS
authors: Sarovich
authors: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
authors: Erin P
authors: http://orcid.org/0000-0002-1079-4882
authors: EP
authors: Price
authors: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
authors: Mirjam
authors: M
authors: Kaestli
authors: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
authors: Mark
authors: M
authors: Mayo
authors: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors: Paul
authors: P
authors: Keim
authors: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia Department of Infectious Diseases and Northern Territory Medical Program, Royal Darwin Hospital, Darwin, Northern Territory, Australia bart.currie@menzies.edu.au.
authors: Bart J
authors: BJ
authors: Currie
mesh_terms: D016957:Burkholderia pseudomallei / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D016358:Contact Tracing; D004196:Disease Outbreaks; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D008554:Melioidosis / Q000382:microbiology* / Q000635:transmission*; D008969:Molecular Sequence Data; D058889:Molecular Typing / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D014871:Water Microbiology; D014881:Water Supply
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