Integration of data from the cell-based ERK1/2 ELISA and the Comparative Toxicogenomics Database deciphers the potential mode of action of bisphenol A and benzo[a]pyrene in lung neoplasm

ABSTRACT Previous attempts to express the toxin complex genes ofPhotorhabdus luminescens W14 inEscherichia coli have failed to reconstitute their oral toxicity to the model insectManduca sexta. Here we show that the combination of three genes, tcdA, tcdB, and tccC, is essential for oral toxicity toM. sexta when expression inE. coli is used. Further, when transcription from native toxin complex gene promoters is used, maximal toxicity in E. coli cultures is associated with the addition of mitomycin C to the growth medium. In contrast, the expression of tcdAB (or the homologoustcaABC operon) with no recombinant tccChomolog in a different P. luminescensstrain, K122, is sufficient to confer oral toxicity on this strain, which is otherwise not orally toxic. We therefore infer thatP. luminescens K122 carries a functionaltccC-like homolog within its own genome, a hypothesis supported by Southern analysis. Recombinant toxins from bothP. luminescens K122 and E.coli were purified as high-molecular-weight particulate preparations. Transmission electron micrograph (TEM) images of these particulate preparations showed that the expression oftcdAB (either with or without tccC) inE. coli produces visible ∼25-nm-long complexes with a head and tail-like substructure. These data are consistent with a model whereby TcdAB constitutes the majority of the complex visible under TEM and TccC either is a toxin itself or is an activator of the complex. The implications for the potential mode of action of the toxin complex genes are discussed.

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Harnessing the Helminth Secretome for Therapeutic Immunomodulators

BioMed Research International ◽

10.1155/2014/964350 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 28

Author(s):

Dana Ditgen ◽

Emmanuela M. Anandarajah ◽

Kamila A. Meissner ◽

Norbert Brattig ◽

Carsten Wrenger ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Mode Of Action ◽

Term Survival ◽

Immune Effector ◽

Host Environment ◽

Autoimmune Inflammatory Disease ◽

Potential Mode ◽

Secretory Products

Helminths are the largest and most complex pathogens to invade and live within the human body. Since they are not able to outpace the immune system by rapid antigen variation or faster cell division or retreat into protective niches not accessible to immune effector mechanisms, their long-term survival depends on influencing and regulating the immune responses away from the mode of action most damaging to them. Immunologists have focused on the excretory and secretory products that are released by the helminths, since they can change the host environment by modulating the immune system. Here we give a brief overview of the helminth-associated immune response and the currently available helminth secretome data. We introduce some major secretome-derived immunomodulatory molecules and describe their potential mode of action. Finally, the applicability of helminth-derived therapeutic proteins in the treatment of allergic and autoimmune inflammatory disease is discussed.

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