Molecular Characterization of Clinical Burkholderia pseudomallei Isolates from India

Mukhopadhyay, Chiranjay; Kaestli, Mirjam; Vandana, Kalwaje Eshwara; Krishna, S.; Mayo, Mark; Richardson, Leisha J.; Tuanyok, Apichai; Keim, Paul; Godoy, Daniel; Spratt, Brian G.; Currie, Bart J.

doi:10.4269/ajtmh.2011.11-0166

Cited by 24 publications

(26 citation statements)

References 11 publications

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“…pseudomallei isolates from India, we previously reported the MLST and MLVA-4 results of seven clinical isolates of B . pseudomallei from patients diagnosed with melioidosis at our settings[10]. In the present study, we furthered our research by including 32 B .…”

Section: Discussionmentioning

confidence: 91%

Unravelling the Molecular Epidemiology and Genetic Diversity among Burkholderia pseudomallei Isolates from South India Using Multi-Locus Sequence Typing

Tellapragada¹,

Kamthan²,

Shaw³

et al. 2016

PLoS ONE

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There is a slow but steady rise in the case detection rates of melioidosis from various parts of the Indian sub-continent in the past two decades. However, the epidemiology of the disease in India and the surrounding South Asian countries remains far from well elucidated. Multi-locus sequence typing (MLST) is a useful epidemiological tool to study the genetic relatedness of bacterial isolates both with-in and across the countries. With this background, we studied the molecular epidemiology of 32 Burkholderia pseudomallei isolates (31 clinical and 1 soil isolate) obtained during 2006–2015 from various parts of south India using multi-locus sequencing typing and analysis. Of the 32 isolates included in the analysis, 30 (93.7%) had novel allelic profiles that were not reported previously. Sequence type (ST) 1368 (n = 15, 46.8%) with allelic profile (1, 4, 6, 4, 1, 1, 3) was the most common genotype observed. We did not observe a genotypic association of STs with geographical location, type of infection and year of isolation in the present study. Measure of genetic differentiation (FST) between Indian and the rest of world isolates was 0.14413. Occurrence of the same ST across three adjacent states of south India suggest the dispersion of B.pseudomallei across the south western coastal part of India with limited geographical clustering. However, majority of the STs reported from the present study remained as “outliers” on the eBURST “Population snapshot”, suggesting the genetic diversity of Indian isolates from the Australasian and Southeast Asian isolates.

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Section: Discussionmentioning

confidence: 91%

Unravelling the Molecular Epidemiology and Genetic Diversity among Burkholderia pseudomallei Isolates from South India Using Multi-Locus Sequence Typing

Tellapragada¹,

Kamthan²,

Shaw³

et al. 2016

PLoS ONE

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“…Once considered endemic to only the dry tropical regions of Australasia and Southeast Asia, this serious disease is now reported more frequently from more regions of the globe (4). While it is clear that more frequent reporting is partially attributable to an increasing awareness of melioidosis in developing nations, evidence is mounting which supports a hypothesis that anthropogenic influences can contribute to the dispersal of melioidosis and its establishment in new regions (5)(6)(7).…”

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confidence: 94%

Biogeography of Burkholderia pseudomallei in the Torres Strait Islands of Northern Australia

et al. 2013

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It has been hypothesized that biogeographical boundaries are a feature of Burkholderia pseudomallei ecology, and they impact the epidemiology of melioidosis on a global scale. This study examined the relatedness of B. pseudomallei sourced from islands in the Torres Strait of Northern Australia to determine if the geography of isolated island communities is a determinant of the organisms' dispersal. Environmental sampling on Badu Island in the Near Western Island cluster recovered a single clone. An additional 32 clinical isolates from the region were sourced. Isolates were characterized using multilocus sequence typing and a multiplex PCR targeting the flagellum gene cluster. Gene cluster analysis determined that 69% of the isolates from the region encoded the ancestral Burkholderia thailandensis-like flagellum and chemotaxis gene cluster, a proportion significantly lower than that reported from mainland Australia and consistent with observations of isolates from southern Papua New Guinea. A goodness-of-fit test indicated that there was geographic localization of sequence types throughout the archipelago, with the exception of Thursday Island, the economic and cultural hub of the region. Sequence types common to mainland Australia and Papua New Guinea were identified. These findings demonstrate for the first time an environmental reservoir for B. pseudomallei in the Torres Strait, and multilocus sequence typing suggests that the organism is not randomly distributed throughout this region and that seawater may provide a barrier to dispersal of the organism. Moreover, these findings support an anthropogenic dispersal hypothesis for the spread of B. pseudomallei throughout this region.

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“…While there are current effective treatment options for Burkholderia infections, there has been increasing concern regarding drug-resistant and naturally resistant strains that render the current treatment regimen ineffective and negatively impact the ability to treat and manage the disease (2,(5)(6)(7). Also, mounting evidence indicates that B. pseudomallei is an emerging pathogen in other areas of the world, and demand for treatment of melioidosis will increase as a result (8)(9)(10)(11)(12). These reasons, along with the ability of Burkholderia to be easily spread via aerosol and ease of dissemination, provide the need to develop novel compounds that inhibit underexploited drug targets.…”

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confidence: 99%

Substituted Diphenyl Ethers as a Novel Chemotherapeutic Platform against Burkholderia pseudomallei

Cummings

Beaupre

Knudson

et al. 2014

Antimicrob Agents Chemother

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bIdentification of a novel class of anti-Burkholderia compounds is key in addressing antimicrobial resistance to current therapies as well as naturally occurring resistance. The FabI enoyl-ACP reductase in Burkholderia is an underexploited target that presents an opportunity for development of a new class of inhibitors. A library of substituted diphenyl ethers was used to identify FabI1-specific inhibitors for assessment in Burkholderia pseudomallei ex vivo and murine efficacy models. Active FabI1 inhibitors were identified in a two-stage format consisting of percent inhibition screening and MIC determination by the broth microdilution method. Each compound was evaluated against the B. pseudomallei 1026b (efflux-proficient) and Bp400 (efflux-compromised) strains. In vitro screening identified candidate substituted diphenyl ethers that exhibited MICs of less than 1 g/ml, and enzyme kinetic assays were used to assess potency and specificity against the FabI1 enzyme. These compounds demonstrated activity in a Burkholderia ex vivo efficacy model, and two demonstrated efficacy in an acute B. pseudomallei mouse infection model. This work establishes substituted diphenyl ethers as a suitable platform for development of novel anti-Burkholderia compounds that can be used for treatment of melioidosis.

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Molecular Characterization of Clinical Burkholderia pseudomallei Isolates from India

Cited by 24 publications

References 11 publications

Unravelling the Molecular Epidemiology and Genetic Diversity among Burkholderia pseudomallei Isolates from South India Using Multi-Locus Sequence Typing

Unravelling the Molecular Epidemiology and Genetic Diversity among Burkholderia pseudomallei Isolates from South India Using Multi-Locus Sequence Typing

Biogeography of Burkholderia pseudomallei in the Torres Strait Islands of Northern Australia

Substituted Diphenyl Ethers as a Novel Chemotherapeutic Platform against Burkholderia pseudomallei

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