Whole-Genome Sequencing Confirms that Burkholderia pseudomallei Multilocus Sequence Types Common to Both Cambodia and Australia Are Due to Homoplasy

Smet, Birgit De; Sarovich, Derek S.; Price, Erin P.; Mayo, Mark; Theobald, Vanessa; Kham, Chun; Heng, Seiha; Phe, Thong; Holden, Matthew T. G.; Parkhill, Julian; Peacock, Sharon J.; Spratt, Brian G.; Jacobs, Jan; Vandamme, Peter; Currie, Bart J.

doi:10.1128/jcm.02574-14

Cited by 43 publications

(62 citation statements)

References 22 publications

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“…We recently reported two situations where B. pseudomallei strains from different countries in different hemispheres had identical STs but were highly divergent on a whole-genome level (21) and an instance where MLST failed to detect a polyclonal infection that was identifiable by WGS (22). Together, these studies demonstrate that MLST can suffer from a lack of discrimination power.…”

Section: Resultsmentioning

confidence: 96%

Tracing Melioidosis Back to the Source: Using Whole-Genome Sequencing To Investigate an Outbreak Originating from a Contaminated Domestic Water Supply

et al. 2015

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c 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. Melioidosis is an underrecognized disease of significant public health burden in many tropical regions across the globe, especially northern Australia and Southeast Asia, where the greatest number of cases are reported annually (1). Melioidosis is caused by the environmental dwelling Gram-negative bacterium Burkholderia pseudomallei, an opportunistic pathogen that most commonly affects people with underlying disease or risk factors, particularly diabetes and hazardous alcohol use (2). Disease severity varies widely and depends on the strain, host immunity, and inoculum size. The highest case fatality rates exceed 90% in septic shock or untreated septic cases (3). Even when appropriate therapy is administered, mortality ranges from 13% in northern Australia (4, 5) to 50% in Southeast Asia (2). In October 2012, B. pseudomallei was upgraded to a tier 1 select agent by the Centers for Disease Control and Prevention (www.selectagents.gov) owing to fears of a deliberate release coupled with the high mortality rate, lack of a vaccine, intrinsic resistance to standard antimicrobial agents, and protean disease presentations that confound diagnosis, particularly in regions where the disease is not endemic.B. pseudomallei infection primarily occurs via percutaneous inoculati...

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Section: Resultsmentioning

confidence: 96%

Tracing Melioidosis Back to the Source: Using Whole-Genome Sequencing To Investigate an Outbreak Originating from a Contaminated Domestic Water Supply

et al. 2015

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“…This extensive lateral gene transfer can confound population analyses, particularly those that are based on studying limited geographic regions (e.g., the Northern Territory, Australia [5]) due to high rates of homoplasy observed among genetic variants. In contrast, genomic analyses of B. pseudomallei populations on a continental scale have revealed a clear separation of B. pseudomallei isolates between Asia and Australia (4,6,7). Bayesian analysis of B. pseudomallei genome variation points to an ancient separation, with migration out of Australia into Asia occurring tens of thousands of years ago during the Pleistocene (4).…”

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Unprecedented Melioidosis Cases in Northern Australia Caused by an Asian Burkholderia pseudomallei Strain Identified by Using Large-Scale Comparative Genomics

Price

Sarovich

Smith

et al. 2016

Appl Environ Microbiol

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Melioidosis is a disease of humans and animals that is caused by the saprophytic bacterium Burkholderia pseudomallei. Once thought to be confined to certain locations, the known presence of B. pseudomallei is expanding as more regions of endemicity are uncovered. There is no vaccine for melioidosis, and even with antibiotic administration, the mortality rate is as high as 40% in some regions that are endemic for the infection. Despite high levels of recombination, phylogenetic reconstruction of B. pseudomallei populations using whole-genome sequencing (WGS) has revealed surprisingly robust biogeographic separation between isolates from Australia and Asia. T he Gram-negative soil-dwelling bacterium Burkholderia pseudomallei is the etiologic agent of melioidosis, an often deadly tropical disease that can be difficult to diagnose, particularly in nonendemic or resource-poor regions where cases are not expected and appropriate microbiological diagnostic tools are not readily available (1). Diabetics are particularly susceptible to melioidosis. B. pseudomallei infection can be acquired from contaminated soil or water by percutaneous inoculation, inhalation, aspiration, or ingestion, and no vaccine targeting this organism is available (2). In 2012, B. pseudomallei was reclassified by U.S. federal agencies as a tier 1 select agent, the highest risk category for a biological entity, due to concerns that this bacterium would pose a severe threat to humans and animals in the event of its deliberate misuse (3).The B. pseudomallei genome exhibits high homologous recombination rates. On a per-allele basis, recombination is estimated to occur between 18 and 30 times more frequently than mutation (4). This extensive lateral gene transfer can confound population analyses, particularly those that are based on studying limited geographic regions (e.g., the Northern Territory, Australia [5]) due to high rates of homoplasy observed among genetic variants. In contrast, genomic analyses of B. pseudomallei populations on a continental scale have revealed a clear separation of B. pseudomallei isolates between Asia and Australia (4, 6, 7). Bayesian analysis of B. pseudomallei genome variation points to an ancient separation, with migration out of Australia into Asia occurring tens of thousands of years ago during the Pleistocene (4). The rarity of pathogen movement is due largely to one factor: new melioidosis cases almost always result from bacterial infection acquired from the local environment, with human-to-human and zoonotic transmission of this pathogen being exceedingly rare (8). In support of the rarity of B. pseudomallei movement across major biogeographic boundaries, the definitive transmission of B. pseudomallei from Asia into Australia has not yet been observed. Nevertheless, melioidosis cases imported into nonendemic locations via travelers are being increasingly reported, as is recognition of locations that are endemic for melioidosis outside the classical regions of Southeast Asia and Australia (9). With modern global tra...

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“…However, for both these STs, isolates from Australia and Cambodia were found to be widely divergent at the whole-genome level, indicating that they were unrelated and the MLST identity represented homoplasy. 8 Within Australia, some genetic population structure among different locations has been detected. In particular, there are no shared environmental STs between the Northern Territory and Queensland.…”

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Burkholderia pseudomallei Genotype Distribution in the Northern Territory, Australia

Chapple

Price

Sarovich

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Melioidosis is a tropical disease of high mortality caused by the environmental bacterium, Burkholderia pseudomallei. We have collected clinical isolates from the highly endemic Northern Territory of Australia routinely since 1989, and animal and environmental B. pseudomallei isolates since 1991. Here we provide a complete record of all B. pseudomallei multilocus sequence types (STs) found in the Northern Territory to date, and distribution maps of the eight most common environmental STs. We observed surprisingly restricted geographic distributions of STs, which is contrary to previous reports suggesting widespread environmental dissemination of this bacterium. Our data suggest that B. pseudomallei from soil and water does not frequently disperse long distances following severe weather events or by migration of infected animals.

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Whole-Genome Sequencing Confirms that Burkholderia pseudomallei Multilocus Sequence Types Common to Both Cambodia and Australia Are Due to Homoplasy

Cited by 43 publications

References 22 publications

Tracing Melioidosis Back to the Source: Using Whole-Genome Sequencing To Investigate an Outbreak Originating from a Contaminated Domestic Water Supply

Tracing Melioidosis Back to the Source: Using Whole-Genome Sequencing To Investigate an Outbreak Originating from a Contaminated Domestic Water Supply

Unprecedented Melioidosis Cases in Northern Australia Caused by an Asian Burkholderia pseudomallei Strain Identified by Using Large-Scale Comparative Genomics

Burkholderia pseudomallei Genotype Distribution in the Northern Territory, Australia

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