<i>In silico</i>identification of metabolic enzyme drug targets in<i>Burkholderia pseudomallei</i>

Challacombe, Jean F.

doi:10.1101/034306

Cited by 3 publications

(4 citation statements)

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ Previous studies have described associations between adaptive metabolism and pathogenesis in intracellular pathogens such as Listeria monocytogenes, Shigella flexneri, Salmonella spp., M. tuberculosis, and B. pseudomallei [37][38][39][40][41][42] ; these findings are consistent with our proteomic results. Arginine deiminase was upregulated in both the passaged B. pseudomallei strain HBPUB15305A and reference strain K96243; this is an enzyme involved in amino-acid metabolism, which may allow passaged B. pseudomallei to use amino acids as an energy source, thus enhancing bacterial survival.…”

Section: Discussionsupporting

confidence: 92%

“…The ability of B. pseudomallei to adapt its metabolic pathways for survival was demonstrated in a previous report 37 . Challacombe et al demonstrated that B. pseudomallei could utilize a wide variety of substrates, including carbohydrates, lipids, glycolipids, dicarboxylic acids, and amino acids during host cell infection.…”

Section: Discussionmentioning

confidence: 79%

“…Challacombe et al demonstrated that B. pseudomallei could utilize a wide variety of substrates, including carbohydrates, lipids, glycolipids, dicarboxylic acids, and amino acids during host cell infection. This indicated the capacity of B. pseudomallei to adjust its metabolism for survival in the presence of a variety of carbon sources 37 . In our study, we also observed altered expression of metabolic proteins that play major roles in carbohydrate and amino acid metabolic pathways in both passaged B. pseudomallei strains.…”

Section: Discussionmentioning

confidence: 99%

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In vitro passage alters virulence, immune activation and proteomic profiles of Burkholderia pseudomallei

Duangurai

Reamtong

Rungruengkitkun

et al. 2020

Sci Rep

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Serial passage is a problem among many bacterial species, especially those where strains have been stored (banked) for several decades. Prior to banking with an organization such as ATCC, many bacterial strains were passaged for many years, so the characteristics of each strain may be extremely different. This is in addition to any differences in the original host environment. For Burkholderia pseudomallei, the number of serial passages should be carefully defined for each experiment because it undergoes adaptation during the course of serial passages. In the present study, we found that passaged B. pseudomallei fresh clinical isolates and reference strain in Luria-Bertani broth exhibited increased plaque formation, invasion, intracellular replication, Galleria mellonella killing abilities, and cytokine production of host cells. These bacteria also modulated proteomic profiles during in vitro passage. We presume that the modulation of protein expression during in vitro passage caused changes in virulence and immunogenicity phenotypes. Therefore, we emphasize the need for caution regarding the use of data from passaged B. pseudomallei. These findings of phenotypic adaptation during in vitro serial passage can help researchers working on B. pseudomallei and on other species to better understand disparate findings among strains that have been reported for many years. Burkholderia pseudomallei is a Gram-negative facultative intracellular bacterium and the causative agent of melioidosis, a life threatening disease in humans and animals 1-3. Melioidosis is an important health problem due to poor understanding of the disease process, frequency of misdiagnosis, and lack of effective vaccination 4,5. Therefore, B. pseudomallei clinical and laboratory isolates have been extensively used to investigate pathogenic mechanisms of bacteria contributing to the disease. Serial passages are routinely performed to maintain an active culture or expand the bacterial number. Serial passages may influence bacterial adaptation through genotypic and phenotypic alterations. In a closely related organism, Burkholderia mallei, genome alterations (e.g. gene insertions, deletions, and repetitive sequences) were observed during in vitro passage 6. However, minimal information has been published regarding B. pseudomallei adaptation during serial passage. U' Ren et al. examined genomic mutations in B. pseudomallei that was serially passaged in vitro for 10 days; they found that tandem repeat genome mutations occurred, and suggested that these tandem repeat regions may contribute to generation and maintenance of adaptive genomic variation in B. pseudomallei 7. It was suggested that these tandem repeat regions may play role in generating and maintaining adaptive genomic variation in B. pseudomallei 7. It is likely that B. pseudomallei has an unstable genome 7 , which could be beneficial for bacterial adaptation and evolution. In addition, Price et al. characterized tandem repeat genome mutations in B. pseudomallei isolates from multiple body sites...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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In vitro passage alters virulence, immune activation and proteomic profiles of Burkholderia pseudomallei

Duangurai

Reamtong

Rungruengkitkun

et al. 2020

Sci Rep

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“…The transcriptome reveals which genes are expressed/repressed and contribute to the phenotype, allowing inference from the genome landscape (which could be aberrant due to DNA mutations or chromosomal rearrangements) [4]. If the expressed genes encode metabolic enzymes, then such expression levels could directly help to understand an increase in activity of a metabolic pathway and aid in the discovery of drug targets for diseased cells, amenable to pharmacological inhibition [5,6]. Similarly, aberrantly expressed genes which encode non-enzymatic proteins may also be reflective of aberrant metabolism within a diseased cell or sub-cellular niche, albeit indirectly [7].…”

Section: Introductionmentioning

confidence: 99%

Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues

et al. 2021

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The integration of untargeted metabolomics and transcriptomics from the same population of cells or tissue enhances the confidence in the identified metabolic pathways and understanding of the enzyme–metabolite relationship. Here, we optimised a simultaneous extraction method of metabolites/lipids and RNA from ependymoma cells (BXD-1425). Relative to established RNA (mirVana kit) or metabolite (sequential solvent addition and shaking) single extraction methods, four dual-extraction techniques were evaluated and compared (methanol:water:chloroform ratios): cryomill/mirVana (1:1:2); cryomill-wash/Econospin (5:1:2); rotation/phenol-chloroform (9:10:1); Sequential/mirVana (1:1:3). All methods extracted the same metabolites, yet rotation/phenol-chloroform did not extract lipids. Cryomill/mirVana and sequential/mirVana recovered the highest amounts of RNA, at 70 and 68% of that recovered with mirVana kit alone. sequential/mirVana, involving RNA extraction from the interphase of our established sequential solvent addition and shaking metabolomics-lipidomics extraction method, was the most efficient approach overall. Sequential/mirVana was applied to study a) the biological effect caused by acute serum starvation in BXD-1425 cells and b) primary ependymoma tumour tissue. We found (a) 64 differentially abundant metabolites and 28 differentially expressed metabolic genes, discovering four gene-metabolite interactions, and (b) all metabolites and 62% lipids were above the limit of detection, and RNA yield was sufficient for transcriptomics, in just 10 mg of tissue.

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Metabolic Modeling of Cystic Fibrosis Airway Microbiota from Patient Samples

Vyas¹

2021

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In silicoidentification of metabolic enzyme drug targets inBurkholderia pseudomallei

Cited by 3 publications

References 192 publications

In vitro passage alters virulence, immune activation and proteomic profiles of Burkholderia pseudomallei

In vitro passage alters virulence, immune activation and proteomic profiles of Burkholderia pseudomallei

Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues

Metabolic Modeling of Cystic Fibrosis Airway Microbiota from Patient Samples

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