Epidemiological Tracking and Population Assignment of the Non-Clonal Bacterium, Burkholderia pseudomallei

Abstract

Rapid assignment of bacterial pathogens into predefined populations is an important first step for epidemiological tracking. For clonal species, a single allele can theoretically define a population. For non-clonal species such as Burkholderia pseudomallei, however, shared allelic states between distantly related isolates make it more difficult to identify population defining characteristics. Two distinct B. pseudomallei populations have been previously identified using multilocus sequence typing (MLST). These populations correlate with the major foci of endemicity (Australia and Southeast Asia). Here, we use multiple Bayesian approaches to evaluate the compositional robustness of these populations, and provide assignment results for MLST sequence types (STs). Our goal was to provide a reference for assigning STs to an established population without the need for further computational analyses. We also provide allele frequency results for each population to enable estimation of population assignment even when novel STs are discovered. The ability for humans and potentially contaminated goods to move rapidly across the globe complicates the task of identifying the source of an infection or outbreak. Population genetic dynamics of B. pseudomallei are particularly complicated relative to other bacterial pathogens, but the work here provides the ability for broad scale population assignment. As there is currently no independent empirical measure of successful population assignment, we provide comprehensive analytical details of our comparisons to enable the reader to evaluate the robustness of population designations and assignments as they pertain to individual research questions. Finer scale subdivision and verification of current population compositions will likely be possible with genotyping data that more comprehensively samples the genome. The approach used here may be valuable for other non-clonal pathogens that lack simple group-defining genetic characteristics and provides a rapid reference for epidemiologists wishing to track the origin of infection without the need to compile population data and learn population assignment algorithms.

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

“…Other studies have since affirmed the ancestral nature of Australian B. pseudomallei and the rare historical transmission of B. pseudomallei from Australia to Asia (6,15). The ancient separation of these two populations has enabled a strong phylogeographic signal between Asian and Australian clades to evolve despite high levels of recombination across the B. pseudomallei genome (4,6). The clarity of this geographic signal is a consequence of both localized evolution and the rarity of transmission, and thus gene flow, between B. pseudomallei strains from these regions.…”

“…The Wallace Line is a major biogeographic barrier between Asia and Australia that has led to restricted genetic flow among the flora and fauna between these two regions. Other studies have since affirmed the ancestral nature of Australian B. pseudomallei and the rare historical transmission of B. pseudomallei from Australia to Asia (6,15). The ancient separation of these two populations has enabled a strong phylogeographic signal between Asian and Australian clades to evolve despite high levels of recombination across the B. pseudomallei genome (4,6).…”

“…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).…”

Burkholderia pseudomallei Genotype Distribution in the Northern Territory, Australia

“…In particular, there is a clear and robust phylogenetic division between Australian and southeast Asian strains, [5][6][7] with almost no overlap between the environmental strains found in Australia and those in southeast Asia. An apparent exception was the presence of two multilocus sequence typing (MLST) sequence types (STs) common to both Australian and Cambodian B. pseudomallei strains (ST-105 and ST-849).…”

Bioinformatics in bacterial molecular epidemiology and public health: databases, tools and the next-generation sequencing revolution

“…More recently, BAPS was also adapted to detect and represent recombination between different populations and subpopulations [46] using MLST sequences as input. These methodologies can provide a much finer picture of how the phenomena shaping population structure interact and how they influence the final population [47][48][49], but the computational needs and complex analysis of results still limit their application in the field of bacterial epidemiology.…”