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Enzymatic degradation of organophosphorus insecticides decreases toxicity in planarians and enhances survival.

ABSTRACT: Organophosphorus insecticides (OPs) are toxic compounds used for agricultural purposes and responsible for severe types of contamination worldwide. OPs may also induce chronic deleterious effects and developmental disruption. Finding remediation strategies is a major concern to diminish their impact on environment and human health. Enzymes have emerged as a promising eco-friendly route for decontaminating OPs. The enzyme SsoPox from the archaea Sulfolobus solfataricus has been particularly studied, considering both its tremendous stability and phosphotriesterase activity. However, the toxicity of the degradation products generated through enzyme hydrolysis has been poorly investigated. To address both neurotoxicity and developmental perturbation, freshwater planarians from Platyhelminthes were considered to evaluate the impact of OP and degradation product exposure. Planarians have a large proportion of stem cells that give them an unconventional capacity for regeneration. OPs were found to be highly toxic to planarians and enzyme decontamination drastically enhanced survival rate. Although not completely innocuous, the degradation products were found to be less toxic than insecticides and reduced poisoning effects by increasing NOEC values by up to eight-fold. SsoPox also limited detrimental consequences on planarian mobility and enabled them to recover a non-exposed type regeneration process suggesting that enzymatic decontamination is a promising alternative to bioremediation.

SUBMITTER: Poirier L

PROVIDER: S-EPMC5680213 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.

Project description:UNLABELLED:Diverse bacteria, including several Pseudomonas species, produce a class of redox-active metabolites called phenazines that impact different cell types in nature and disease. Phenazines can affect microbial communities in both positive and negative ways, where their presence is correlated with decreased species richness and diversity. However, little is known about how the concentration of phenazines is modulated in situ and what this may mean for the fitness of members of the community. Through culturing of phenazine-degrading mycobacteria, genome sequencing, comparative genomics, and molecular analysis, we identified several conserved genes that are important for the degradation of three Pseudomonas-derived phenazines: phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and pyocyanin (PYO). PCA can be used as the sole carbon source for growth by these organisms. Deletion of several genes in Mycobacterium fortuitum abolishes the degradation phenotype, and expression of two genes in a heterologous host confers the ability to degrade PCN and PYO. In cocultures with phenazine producers, phenazine degraders alter the abundance of different phenazine types. Not only does degradation support mycobacterial catabolism, but also it provides protection to bacteria that would otherwise be inhibited by the toxicity of PYO. Collectively, these results serve as a reminder that microbial metabolites can be actively modified and degraded and that these turnover processes must be considered when the fate and impact of such compounds in any environment are being assessed. IMPORTANCE:Phenazine production by Pseudomonas spp. can shape microbial communities in a variety of environments ranging from the cystic fibrosis lung to the rhizosphere of dryland crops. For example, in the rhizosphere, phenazines can protect plants from infection by pathogenic fungi. The redox activity of phenazines underpins their antibiotic activity, as well as providing pseudomonads with important physiological benefits. Our discovery that soil mycobacteria can catabolize phenazines and thereby protect other organisms against phenazine toxicity suggests that phenazine degradation may influence turnover in situ. The identification of genes involved in the degradation of phenazines opens the door to monitoring turnover in diverse environments, an essential process to consider when one is attempting to understand or control communities influenced by phenazines.

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Enzymatic degradation of organophosphorus insecticides decreases toxicity in planarians and enhances survival.

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