Effects of microbial mitochondriotoxins from food and indoor air on mammalian cells
Year: 2016
Type: dissertation
Abstract: Humans are exposed to microbes and microbial compounds continuously via environmental exposure and food in addition to our own microbiome. This thesis reports new empirical findings concerning the types of mitochondrial toxins present in food and indoor air and the effects of these toxins on mammalian cells. Dust and aerosolized compounds collected from moisture-damaged buildings were shown to have mitochondriotoxic effects detectable with a boar sperm motility inhibition (BSMI) assay. Toxin-producing bacteria isolated from the dusts and aerosols included producers of the mitochondrial toxins amylosin, cereulide, and valinomycin. In addition, aerosolized valinomycin and toxic chemical compounds emitted from building materials were detected using boar spermatozoa, demonstrating that the BMSI assay could be used to screen for mitochondrial toxicity in indoor air. Amylosin, a mitochondriotoxin produced by Bacillus spp. from indoor air and food, was shown to be immunotoxic: exposure of human primary macrophages to nanomolar concentrations of amylosin stimulated the release of inflammatory cytokines interleukin 1β and interleukin 18. Amylosin is the first bacterial channel-forming ionophore toxin reported to have this effect. Low amounts of amylosin caused significant dose-dependent potassium ion efflux from human somatic cells and boar spermatozoa. Potassium efflux may be the trigger causing the observed cytokine release from macrophages after amylosin exposure. Amylosin also displayed antifungal and antibacterial activity which may give its producers a competitive advantage in mixed microbial communities. Two previously unreported food safety hazards were identified from cereal grains. A novel heat-stable mitochondrial toxin named paenilide, similar to cereulide biochemically and in mode of action, was found to be produced by Paenibacillus tundrae isolated from barley grains. This finding shows that the genus Paenibacillus cannot be considered harmless for human health. Paenilide consisted of two components with molecular masses equal to those of cereulide and homocereulide but with longer chromatographic retention times, indicating more hydrophobic structures than those of the cereulide compounds. Paenilide acted as a lipophilic potassium ionophore, causing depolarization, swelling, uncoupling of oxidative phosphorylation, and loss of respiratory control in isolated rat liver mitochondria. Paenilide accelerated glucose consumption in porcine kidney epithelial cells, causing metabolic acidosis, and was cytotoxic to porcine and murine cells. Paenilide was as toxic as cereulide at nanomolar amounts, making it a possibly potent food poisoning agent. Paenilide was produced at incubation temperatures down to +5°C, indicating potential toxin formation in chilled foods. The second novel finding connected to cereal grains was the discovery of toxin-producing Streptomyces spp. in healthy-looking grains of barley and spring wheat. The barley grain isolates, belonging to the Streptomyces albidoflavus group, produced the mitochondriotoxic macrolide antimycin A, a known disrupter of oxidative phosphorylation. The cause of the mitochondrial toxicity of the spring wheat grain isolates, most closely related to Streptomyces sedi, remained unidentified. The toxicity of the isolates and grains was detected using the BSMI assay, which was sensitive enough to detect nanomolar contamination corresponding to 2 ng of antimycin A per barley grain. Antimycin A was more toxic towards porcine kidney epithelial cells than the mycotoxin enniatin B but less toxic than cereulide or paenilide. Exposure of porcine kidney epithelial cells to these four toxins accelerated glucose consumption and caused mitochondrial depolarization, indicating upregulation of glycolysis. Pancreatic insulin-producing beta cells, however, are not able to switch to glycolytic ATP production and undergo necrotic cell death upon exposure to mitochondrial toxins. Thus, consumption of grains contaminated with mitochondrial toxins may especially affect pancreatic functions. In conlusion, the results of this thesis show that chronic exposure via indoor air or food to sub-lethal concentrations of mitochondriotoxins produced by spore-forming bacteria may be more common than known so far. This exposure may connect to the increasing worldwide incidence of western lifestyle diseases, such as diabetes, asthma, and allergies as well as cardiovascular and neurological disorders. The studied toxins are all heat-stable and produced by spore-formers able to withstand harsh environmental conditions, highlighting that preventing their presence and endurance in food and indoor environments is problematic.
Source: Työväentutkimus Vuosikirja
Author: Stiina Rasimus-Sahari
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2245597084