Burkholderia pseudomallei , a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of B. pseudomallei infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across B. pseudomallei strains. We previously characterized B. pseudomallei strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical B. pseudomallei isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in B. pseudomallei and Burkholderia mallei , but not Burkholderia thailandensis . Genes encoding known B. pseudomallei virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding B. pseudomallei pathogenicity to guide the design of new therapeutics for treating melioidosis.
A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity.
Materials and methods:Here, we utilized the Caenorhabditis elegans-P. aeruginosa 43 infection model to assess the anti-infective properties of H. atra. We conducted the C. 44 elegans-P. aeruginosa slow killing assay to isolate a fraction with capable of conferring 45 survival to pathogen-infected worms, followed by a series of tests to assess the 46 anti-virulence and immune-related properties of the sea cucumber bioactive fraction. 47 Results: The H. atra methanol extract improved survival of infected worms without 48 affecting pathogen viability. Further extraction and assays sequestered a fraction with 49 significant anti-infective activities and was able to attenuate the secretion of virulence 50 factors and biofilm formation. Treatment of P. aeruginosa-infected transgenic lys-7::GFP 51 worms with this fraction also restored the repressed expression of host lys-7, a defense 52 enzyme. QTOF-LCMS analysis of this fraction revealed the presence of 53 aspidospermatidine, an indole alkaloid and inosine. 54 Conclusion: Collectively, results shows that H. atra confers survival advantage against P. 55 aeruginosa infection through inhibition of pathogen virulence and the restitution of host 56 lys-7 expression.57
The early development of the American fatty acid industry during 1900–1920 is usually associated with the use of stearic acid in candles for lighting purposes. Today, the use of stearic acid in candle manufacture continues; the volume consumed for this application is not small, but the use is for ornamental, decorative or festival purposes, only incidentally for emergency lighting purposes. When one consideres that most condles consist of 10–20% stearic acid, which improves among other things, the appearance, burning qualities and stiffness of the candle, the volume consumed is appreciable. More than that, the growth rate in this use is impressive. In 1965, it has been estimated that the volume of double‐pressed stearic acid that found its wya into candles was 3.5 million pounds. Today (1979) it is conservatively estimated that from 10–12 million pounds are utilized for this purpose. Innovations, such as the development of driples candles, achieved by the incorporation of a somewhat larger proportion of stearic acid to the external wax coat, are now possible uses. Concrete and asphalt are examples of much‐used large tonnage materials of construction which have disadvantages in use that can be at least partially or significantly improved through the incorporation of stearic acid or certain other fatty chemicals. An excellent example of the tailor‐making of fatty acid derivatives to satisfy an almost desperate need is provided by the development of derivatives suited for the retardation of water evaporation from reservoirs in arid areas. In 1966 it was estimated that the evaporation from large lakes and reservoirs in 17 western states was equivalent to 14 million acre feet, an amount which could ordinarily supply 84 million people annually. The design of water insoluble long chain organic compounds with a hydrophilic group at one terminal position gives products capable of forming monomolecular films which are uniquely suited to solve this problem. Fatty alcohol ethoxylates are only one approach among several.
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