The epidemiology and molecular characterization of Burkholderia pseudomallei in Malaysian Borneo
Melioidosis is a potentially fatal disease caused by Burkholderia pseudomallei which is endemic in Malaysian Borneo. The general aim of this study is to elucidate the molecular epidemiology of B. pseudomallei in Malaysian Borneo. Consistent with the Wallace line theory of separation, genotyping s...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2014
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| Subjects: | |
| Online Access: | http://ir.unimas.my/id/eprint/10751/3/Yuwana%20Podin%20ft.pdf |
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| Summary: | Melioidosis is a potentially fatal disease caused by Burkholderia pseudomallei
which is endemic in Malaysian Borneo. The general aim of this study is to
elucidate the molecular epidemiology of B. pseudomallei in Malaysian Borneo.
Consistent with the Wallace line theory of separation, genotyping showed
Malaysian Borneo clinical B. pseudomallei isolates were more related to
Southeast Asian strains than to Australian strains. Whole genome sequencing
demonstrated that B. pseudomallei from Sarawak were very closely related to
each other. Biochemical testing using VITEK 2 revealed that 25% of B.
pseudomallei from Malaysian Borneo were misidentified as B. cepacia,
suggesting that specificity of that identification system is regionally dependent. A
major and unexpected finding was that 88% of Sarawak B. pseudomallei were
gentamicin susceptible, with these B. pseudomallei being restricted to multilocus
sequence type ST881 and its single locus variant ST997. A novel nonsynonymous
mutation was identified within amrB, an essential component of the
AmrAB-OprA multi-drug efflux pump. Reversion of the mutation to the wild-type
sequence confirmed the role of this mutation in conferring aminoglycoside and
macrolide sensitivity. No environmental B. pseudomallei were isolated from
Sarawak but other Burkholderia species were isolated, prompting the formulation
of hypotheses to explain the lack of environmental B. pseudomallei. Although
inconclusive, experiments showed antagonistic activities by other environmental
Burkholderia spp. recovered from environmental sampling studies towards B.
pseudomallei and also that gentamicin susceptible B. pseudomallei were slightly
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less robust than gentamicin resistant strains in competing with other soil
microorganisms. This thesis contributed to the understanding of the population
structure of B. pseudomallei in Malaysian Borneo, Southeast Asia and globally.
The discovery of gentamicin susceptibility in Sarawak B. pseudomallei has
significant implications for laboratory diagnosis and environmental sampling of B.
pseudomallei in Malaysian Borneo and potentially in other melioidosis endemic
regions. Although the exact distributions, quantification and potential
environmental hazards and implications of B. pseudomallei in Malaysian Borneo
remain uncertain, these studies have led to important research questions now to be
explored. Most immediate is further searching for the proposed existence of an as
yet unidentified localized niche of B. pseudomallei in Malaysian Borneo. |
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