ABSTRACT
Bongkrekic acid (BKA) produced by pseudomonas cocovenenans is a deadly toxin, and is mainly found in spoiled or fermented foods. However, less is known on its immunotoxicity. Neutrophil extracellular traps (NETs) are a novel effector mechanism of neutrophils against invading pathogens, but excessive NETs also contribute to tissue damage. This study aimed to investigate NET formation triggered by BKA in murine neutrophils, and describe its characteristics and potential mechanisms. Our results showed that BKA triggered NET formation via co-localization of DNA and histone or MPO by immunostaining. Moreover, BKA-triggered NET formation was dose- and time-dependent via NET quantification based on Picogreen-derived fluorescence intensities. Furthermore, BKA increased ROS production in neutrophils. Pharmacological inhibition indicated that BKA-triggered NET formation was associated with ROS-p38 and -ERK signaling pathways, but independent on NADPH oxidase. Besides, PAD4 and P2X1 receptor also mediated BKA-triggered NET formation. To our knowledge, all these findings provide for the first time an initial understanding of BKA on innate immunity, which might be helpful for further investigation on BKA immunotoxicity.
Subject(s)
Bongkrekic Acid/toxicity , Extracellular Traps/metabolism , Neutrophils/metabolism , Protein-Arginine Deiminase Type 4/metabolism , Receptors, Purinergic P2X1/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Anti-Bacterial Agents/toxicity , Dose-Response Relationship, Drug , Extracellular Traps/drug effects , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Male , Mice , Mice, Inbred BALB C , Neutrophils/drug effectsABSTRACT
In January 2015, 75 people died and 177 were hospitalized in the Mozambique village of Chitima after attending a funeral. The deaths were linked to the consumption of a traditional African beverage called pombe. Samples of the suspect pombe were subjected to myriad analyses and compared to a control sample. Ultimately, non-targeted liquid chromatography-mass spectrometry screening revealed the presence of the potent toxin bongkrekic acid, and its structural isomer, isobongkrekic acid. Quantitative analysis found potentially fatal levels of these toxins in the suspect pombe samples. Bongkrekic acid is known to be produced by the bacterium Burkholderia gladioli pv. cocovenenans. This bacterium could not be isolated from the suspect pombe, but bacteria identified as B. gladioli were isolated from corn flour, a starting ingredient in the production of pombe, obtained from the brewer's home. When the bacteria were co-plated with the fungus Rhizopus oryzae, which was also isolated from the corn flour, synergistic production of bongkrekic acid was observed. The results suggest a mechanism for bongkrekic acid intoxication, a phenomenon previously thought to be restricted to specific regions of Indonesia and China.
Subject(s)
Beer/adverse effects , Bongkrekic Acid/toxicity , Burkholderia gladioli/isolation & purification , Bongkrekic Acid/analysis , Burkholderia gladioli/pathogenicity , Chromatography, Liquid , Disease Outbreaks , Flour/microbiology , Humans , Mass Spectrometry , MozambiqueABSTRACT
Bongkrekic acid causes fatal food poisoning which is associated with hyperglycaemia. Here we demonstrate that bongkrekic acid, a potent inhibitor of the mitochondrial ATP/ADP translocase, inhibits glucose-induced electrical activity in the pancreatic beta-cell through the stimulation of ATP-sensitive potassium channel (K-ATP-channel) activity. By comparison of its effects with those of oligomycin, we suggest that bongkrekic acid acts by the inhibition of glucose metabolism and may induce hyperglycaemia by impairing beta-cell function.
Subject(s)
Bongkrekic Acid/toxicity , Islets of Langerhans/drug effects , Membrane Potentials/drug effects , Mitochondrial ADP, ATP Translocases/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Animals , Islets of Langerhans/enzymology , Islets of Langerhans/physiology , Mice , Mitochondria/enzymology , Potassium Channels/drug effectsABSTRACT
Fermented corn flour containing toxoflavin and bongkretic acid produced by P. farinofermentans can cause acute food poisoning, but study on mutagenicity of toxoflavin has not been reported. We studied the mutagenicity of toxoflavin by Tradescantia Paludosa and animal micronucleus tests. The results showed that toxoflavin possesses distinct mutagenic action in both plant and animal cells. Mutagenic action of toxoflavin in cells may have important bearing on food hygiene examination.
