Detection of Burkholderia pseudomallei toxin-mediated inhibition of protein synthesis using a Caenorhabditis elegans ugt–29 biosensor

Abstract

Toxins are believed to play a crucial role in Burkholderia pseudomallei pathogenicity, however to date, only a few have been identified. The discovery of additional toxic molecules is limited by the lack of a sensitive indicator of B. pseudomallei toxicity. Previously, from a whole genome transcriptome analysis of B. pseudomallei-infected Caenorhabditis elegans, we noted significant overexpression of a number of worm genes encoding detoxification enzymes, indicating the host’s attempt to clear bacterial toxic molecules. One of these genes, ugt–29, a family member of UDP-glucuronosyltransferases, was the most robustly induced phase II detoxification gene. In this study, we show that strong induction of ugt–29 is restricted to infections by the most virulent species among the pathogens tested. We also noted that ugt–29 is activated upon disruption of host protein synthesis. Hence, we propose that UGT–29 could be a promising biosensor to detect B. pseudomallei toxins that compromise host protein synthesis. The identification of bactobolin, a polyketide-peptide hybrid molecule, as a toxic molecule of B. pseudomallei further verifies the utilization of this surveillance system to search for bacterial toxins. Hence, a ugt–29 based reporter should be useful in screening for other molecules that inhibit host protein synthesis.

Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing

“…We used a Caenorhabditis elegans infection model to test whether malleilactone contributes to B. pseudomallei virulence. Previous studies indicate that B. pseudomallei rapidly kills C. elegans through production of several secreted toxins, although only one has been identified (11,(23)(24)(25)(26). Toxins also appear to be a significant contributor to B. pseudomallei pathogenicity in mammalian infections (6,7).…”

“…Some of these gene clusters are also present in B. thailandensis, which has been used as a surrogate in some cases (8)(9)(10). Some of the clusters have been studied directly in B. pseudomallei, particularly those that are not shared in B. thailandensis (6,7,(11)(12)(13). In many cases, no polyketide products, or very low concentrations, are synthesized in standard laboratory conditions, making them difficult to identify and study.…”

UDP-Glucosyltransferases Induced by Nosema bombycis Provide Resistance to Microsporidia in Silkworm (Bombyx mori)

“…Besides response to insecticides, UGT genes are also a response to pathogens. Caenorhabditis elegans UGT29 was robustly induced by Burkholderia pseudomallei [ 64 ]. Unlike Caenorhabditis elegans, there are no reports about the involvement of UGT in microbial stress response in insects.…”

The role of charge in the toxicity of polymer-coated cerium oxide nanomaterials to Caenorhabditis elegans

“…ALH-1 is a mitochondrial protein that oxidizes aldehydes to carboxylic acids for aldehyde metabolism, and this activity is part of the biological detoxification process (Vasiliou et al, 2000). EEF-2 is important in the elongation phase of protein synthesis, and it is required for embryogenesis and vulval morphogenesis (Wong et al, 2016). Protein synthesis is energetically costly, and reductions to protein synthesis and metabolic activity have been linked with increased lifespan and stress resistance due to decrease in toxic metabolic byproducts and increased energy savings that can be reallocated to cellular maintenance and repair (Hansen et al, 2007).…”