Several species of Dinophysis produce one or two groups of lipophilic toxins: okadaic acid (OA) and its derivatives; or the dinophysistoxins (DTXs) (also known as diarrhetic shellfish poisons or DSP ...toxins) and pectenotoxins (PTXs). DSP toxins are potent inhibitors of protein phosphatases, causing gastrointestinal intoxication in consumers of contaminated seafood. Forty years after the identification of Dinophysis as the causative agent of DSP in Japan, contamination of filter feeding shellfish exposed to Dinophysis blooms is recognized as a problem worldwide. DSP events affect public health and cause considerable losses to the shellfish industry. Costly monitoring programs are implemented in regions with relevant shellfish production to prevent these socioeconomic impacts. Harvest closures are enforced whenever toxin levels exceed regulatory limits (RLs). Dinophysis species are kleptoplastidic dinoflagellates; they feed on ciliates (Mesodinium genus) that have previously acquired plastids from cryptophycean (genera Teleaulax, Plagioselmis, and Geminigera) nanoflagellates. The interactions of Dinophysis with different prey regulate their growth and toxin production. When Dinophysis cells are ingested by shellfish, their toxins are partially biotransformed and bioaccumulated, rendering the shellfish unsuitable for human consumption. DSP toxins may also affect shellfish metabolism. This book covers diverse aspects of the abovementioned topics—from the laboratory culture of Dinophysis and the kinetics of uptake, transformation, and depuration of DSP toxins in shellfish to Dinophysis population dynamics, the monitoring and regulation of DSP toxins, and their impact on the shellfish industry in some of the aquaculture regions that are traditionally most affected, namely, northeastern Japan, western Europe, southern Chile, and New Zealand.
Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors
. One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins ...directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the full range of growth inhibitory mechanisms remains unknown
. Here we identify a type VI secretion effector, Tas1, in the opportunistic pathogen Pseudomonas aeruginosa. The crystal structure of Tas1 shows that it is similar to enzymes that synthesize (p)ppGpp, a broadly conserved signalling molecule in bacteria that modulates cell growth rate, particularly in response to nutritional stress
. However, Tas1 does not synthesize (p)ppGpp; instead, it pyrophosphorylates adenosine nucleotides to produce (p)ppApp at rates of nearly 180,000 molecules per minute. Consequently, the delivery of Tas1 into competitor cells drives rapid accumulation of (p)ppApp, depletion of ATP, and widespread dysregulation of essential metabolic pathways, thereby resulting in target cell death. Our findings reveal a previously undescribed mechanism for interbacterial antagonism and demonstrate a physiological role for the metabolite (p)ppApp in bacteria.
Abstract
Cyanobacteria produce an unparalleled variety of toxins that can cause severe health problems or even death in humans, and wild or domestic animals. In the last decade, biosynthetic pathways ...have been assigned to the majority of the known toxin families. This review summarizes current knowledge about the enzymatic basis for the production of the hepatotoxins microcystin and nodularin, the cytotoxin cylindrospermopsin, the neurotoxins anatoxin and saxitoxin, and the dermatotoxin lyngbyatoxin. Elucidation of the biosynthetic pathways of the toxins has paved the way for the development of molecular techniques for the detection and quantification of the producing cyanobacteria in different environments. Phylogenetic analyses of related clusters from a large number of strains has also allowed for the reconstruction of the evolutionary scenarios that have led to the emergence, diversification, and loss of such gene clusters in different strains and genera of cyanobacteria. Advances in the understanding of toxin biosynthesis and evolution have provided new methods for drinking-water quality control and may inspire the development of techniques for the management of bloom formation in the future.
We report the biosynthetic pathways of cyanobacterial toxins and describe the evolutionary scenarios that have led to the emergence, diversification and loss of such gene clusters.
Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or type D. ETX belongs to the heptameric β‐pore‐forming toxins including aerolysin and Clostridium septicum ...alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells consisting in a β‐barrel of 14 amphipatic β strands. By contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin and is responsible for enterotoxemia in animals, mainly sheep. ETX induces perivascular edema in various tissues and accumulates in particular in the kidneys and brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood–brain barrier and stimulate the release of glutamate, which accounts for the symptoms of nervous excitation observed in animal enterotoxemia. At the cellular level, ETX causes rapid swelling followed by cell death involving necrosis. The precise mode of action of ETX remains to be determined. ETX is a powerful toxin, however, it also represents a unique tool with which to vehicle drugs into the central nervous system or target glutamatergic neurons.
Clostridium perfringensε‐toxin is a potent lethal toxin, which is responsible for animal enterotoxemia. It is structurally related to aerolysin and Clostridium septicumα‐toxin. These toxins heptamerize, form pores through the plasma membrane, and induce cell necrosis, ε‐toxin being the most potent. ε‐toxin accumulates in the kidneys, passes the blood brain barrier and stimulates the glutamate release
Abstract
Bacillus thuringiensis bacteria are insect pathogens that produce different Cry and Cyt toxins to kill their hosts. Here we review the group of three-domain Cry (3d-Cry) toxins. Expression ...of these 3d-Cry toxins in transgenic crops has contributed to efficient control of insect pests and a reduction in the use of chemical insecticides. The mode of action of 3d-Cry toxins involves sequential interactions with several insect midgut proteins that facilitate the formation of an oligomeric structure and induce its insertion into the membrane, forming a pore that kills midgut cells. We review recent progress in our understanding of the mechanism of action of these Cry toxins and focus our attention on the different mechanisms of resistance that insects have evolved to counter their action, such as mutations in cadherin, APN and ABC transporter genes. Activity of Cry1AMod toxins, which are able to form toxin oligomers in the absence of receptors, against different resistant populations, including those affected in the ABC transporter and the role of dominant negative mutants as antitoxins, supports the hypothesis that toxin oligomerization is a limiting step in the Cry insecticidal activity. Knowledge of the action of 3d-Cry toxin and the resistance mechanisms to these toxins will set the basis for a rational design of novel toxins to overcome insect resistance, extending the useful lifespan of Cry toxins in insect control programs.
The review examined the similarities and differences of the molecular mechanisms and environmental factors that regulate aflatoxin, fumonisin and trichothecene biosynthesis.
Bacterial toxins represent a vast reservoir of biochemical diversity that can be repurposed for biomedical applications. Such proteins include a group of predicted interbacterial toxins of the ...deaminase superfamily, members of which have found application in gene-editing techniques
. Because previously described cytidine deaminases operate on single-stranded nucleic acids
, their use in base editing requires the unwinding of double-stranded DNA (dsDNA)-for example by a CRISPR-Cas9 system. Base editing within mitochondrial DNA (mtDNA), however, has thus far been hindered by challenges associated with the delivery of guide RNA into the mitochondria
. As a consequence, manipulation of mtDNA to date has been limited to the targeted destruction of the mitochondrial genome by designer nucleases
.Here we describe an interbacterial toxin, which we name DddA, that catalyses the deamination of cytidines within dsDNA. We engineered split-DddA halves that are non-toxic and inactive until brought together on target DNA by adjacently bound programmable DNA-binding proteins. Fusions of the split-DddA halves, transcription activator-like effector array proteins, and a uracil glycosylase inhibitor resulted in RNA-free DddA-derived cytosine base editors (DdCBEs) that catalyse C•G-to-T•A conversions in human mtDNA with high target specificity and product purity. We used DdCBEs to model a disease-associated mtDNA mutation in human cells, resulting in changes in respiration rates and oxidative phosphorylation. CRISPR-free DdCBEs enable the precise manipulation of mtDNA, rather than the elimination of mtDNA copies that results from its cleavage by targeted nucleases, with broad implications for the study and potential treatment of mitochondrial disorders.
Toxins of cyanobacteria van Apeldoorn, Marian E.; van Egmond, Hans P.; Speijers, Gerrit J. A. ...
Molecular nutrition & food research,
January 2007, Letnik:
51, Številka:
1
Journal Article
Recenzirano
Blue‐green algae are found in lakes, ponds, rivers and brackish waters throughout the world. In case of excessive growth such as bloom formation, these bacteria can produce inherent toxins in ...quantities causing toxicity in mammals, including humans. These cyanotoxins include cyclic peptides and alkaloids. Among the cyclic peptides are the microcystins and the nodularins. The alkaloids include anatoxin‐a, anatoxin‐a(S), cylindrospermopsin, saxitoxins (STXs), aplysiatoxins and lyngbyatoxin. Both biological and chemical methods are used to determine cyanotoxins. Bioassays and biochemical assays are nonspecific, so they can only be used as screening methods. HPLC has some good prospects. For the subsequent detection of these toxins different detectors may be used, ranging from simple UV‐spectrometry via fluorescence detection to various types of MS. The main problem in the determination of cyanobacterial toxins is the lack of reference materials of all relevant toxins. In general, toxicity data on cyanotoxins are rather scarce. A majority of toxicity data are known to be of microcystin‐LR. For nodularins, data from a few animal studies are available. For the alkaloids, limited toxicity data exist for anatoxin‐a, cylindrospermopsin and STX. Risk assessment for acute exposure could be relevant for some types of exposure. Nevertheless, no acute reference doses have formally been derived thus far. For STX(s), many countries have established tolerance levels in bivalves, but these limits were set in view of STX(s) as biotoxins, accumulating in marine shellfish. Official regulations for other cyanotoxins have not been established, although some (provisional) guideline values have been derived for microcystins in drinking water by WHO and several countries.
This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of ...toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats and biofilms of benthic species. Toxic cyanobacterial populations have been reported in freshwaters in over 45 countries, and in numerous brackish, coastal, and marine environments. The principal toxigenic genera are listed. Known sources of the families of cyanobacterial toxins (hepato-, neuro-, and cytotoxins, irritants, and gastrointestinal toxins) are briefly discussed. Key procedures in the risk management of cyanobacterial toxins and cells are reviewed, including derivations (where sufficient data are available) of tolerable daily intakes (TDIs) and guideline values (GVs) with reference to the toxins in drinking water, and guideline levels for toxigenic cyanobacteria in bathing waters. Uncertainties and some gaps in knowledge are also discussed, including the importance of exposure media (animal and plant foods), in addition to potable and recreational waters. Finally, we present an outline of steps to develop and implement risk management strategies for cyanobacterial cells and toxins in waterbodies, with recent applications and the integration of Hazard Assessment Critical Control Point (HACCP) principles.
In April and May 2011, three dogs died and one dog became ill after swimming in Lake IJmeer (The Netherlands). At the time, the lake was infested with the benthic cyanobacterial species Phormidium. A ...Eurasian Coot (Fulica atra) and a Black-headed Gull (Chroicocephalus ridibundus) also died near Lake IJmeer in the same period. One of the dogs and both birds were subjected to a pathological investigation. Furthermore, the Phormidium mat; algal samples from the dikes; contents of the animals’ digestive systems and organ tissues were analysed for the following cyanobacterial toxins: (homo)anatoxin-a; (7-deoxy-)cylindrospermopsin; saxitoxins and gonyautoxins by LC-MS/MS. Samples were also analysed for the nontoxic (homo)anatoxin-a metabolites dihydro(homo)anatoxin-a and epoxy(homo)anatoxin-a. The dog necropsy results indicated neurotoxicosis and its stomach contained Phormidium filaments. Anatoxin-a was detected in the Phormidium mat (272μgg−1 dry weight, stdev 65, n=3) and in the dog’s stomach contents (9.5μgg−1 dry weight, stdev 2.4, n=3). Both samples also contained the anatoxin-a metabolite dihydroanatoxin-a, and a trace of homoanatoxin-a was detected in the Phormidium mat. The birds were in bad nutritive condition at the time of necropsy and their stomachs and intestines did not contain any cyanobacterial material. Furthermore, no cyanobacterial toxins were detected in their stomachs, intestines and organs and they both had lesions that are not associated with cyanobacterial intoxication. This is the first report of anatoxin-a and homoanatoxin-a occurrence in The Netherlands, these toxins have likely caused the deaths of three dogs. The birds probably died of other causes. Dutch recreational waters are at this moment only screened for pelagic cyanobacterial species, the current bathing water protocol therefore does not protect humans and animals from negative effects of blooms of benthic cyanobacteria.
► In The Netherlands, three dogs died after swimming. ► Clinical symptoms and necropsy pointed towards neurotoxicosis. ► Cyanobacteria and the neurotoxins (homo)anatoxin-a were found in stomach contents. ► Ingestion of the cyanobacterium Phormidium has caused the dogs’ death. ► First report of (homo)anatoxin-a occurrence and poisoning in The Netherlands.
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