Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes

© 2016, Springer-Verlag Berlin Heidelberg.Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of acetylcholinesterase, a key enzyme in central and peripheral nervous systems. Numerous approaches, including chemical, physical, and biological decontamination, have been considered for developing decontamination methods against organophosphates (OPs). This work is an overview of both validated and emerging strategies for the protection against OP pollution with special attention to the use of decontaminating enzymes. Considerable efforts have been dedicated during the past decades to the development of efficient OP degrading biocatalysts. Among these, the promising biocatalyst SsoPox isolated from the archaeon Sulfolobus solfataricus is emphasized in the light of recently published results. This hyperthermostable enzyme appears to be particularly attractive for external decontamination purposes with regard to both its catalytic and stability properties

Organophosphorus poisoning in animals and enzymatic antidotes

© 2018 Springer-Verlag GmbH Germany, part of Springer Nature Organophosphorus compounds (OPs) are neurotoxic molecules developed as pesticides and chemical warfare nerve agents (CWNAs). Most of them are covalent inhibitors of acetylcholinesterase (AChE), a key enzyme in nervous systems, and are therefore responsible for numerous poisonings around the world. Many animal models have been studied over the years in order to decipher the toxicity of OPs and to provide insights for therapeutic and decontamination purposes. Environmental impact on wild animal species has been analyzed to understand the consequences of OP uses in agriculture. In complement, various laboratory models, from invertebrates to aquatic organisms, rodents and primates, have been chosen to study chronic and acute toxicity as well as neurobehavioral impact, immune response, developmental disruption, and other pathological signs. Several decontamination approaches were developed to counteract the poisoning effects of OPs. Among these, enzyme-based strategies are particularly attractive as they allow efficient external decontamination without toxicity or environmental impact and may be of interest for treatment. Approaches using bioscavengers for prophylaxis, treatment, and external decontamination are emphasized and their potential is discussed in the light of toxicological observations from various animal models. The relevance of animal models, regarding their cholinergic system and the abundance of naturally protecting enzymes, is also discussed for better extrapolation of results to human

Genetic diversity and phylogeny of Aedes aegypti, the main arbovirus vector in the Pacific

Background The Pacific region is an area unique in the world, composed of thousands of islands with differing climates and environments. The spreading and establishment of the mosquito Aedes aegypti in these islands might be linked to human migration. Ae. aegypti is the major vector of arboviruses (dengue, chikungunya and Zika viruses) in the region. The intense circulation of these viruses in the Pacific during the last decade led to an increase of vector control measures by local health authorities. The aim of this study is to analyze the genetic relationships among Ae. aegypti populations in this region. Methodology/Principal Finding We studied the genetic variability and population genetics of 270 Ae. aegypti, sampled from 9 locations in New Caledonia, Fiji, Tonga and French Polynesia by analyzing nine microsatellites and two mitochondrial DNA regions (CO1 and ND4). Microsatellite markers revealed heterogeneity in the genetic structure between the western, central and eastern Pacific island countries. The microsatellite markers indicate a statistically moderate differentiation (FST = 0.136; P < = 0.001) in relation to island isolation. A high degree of mixed ancestry can be observed in the most important towns (e.g. Noumea, Suva and Papeete) compared with the most isolated islands (e.g. Ouvea and Vaitahu). Phylogenetic analysis indicated that most of samples are related to Asian and American specimens. Conclusions/Significance Our results suggest a link between human migrations in the Pacific region and the origin of Ae. aegypti populations. The genetic pattern observed might be linked to the island isolation and to the different environmental conditions or ecosystems

Intoxication aux organophosphorés : vers des traitements enzymatiques

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Steady-state kinetics of enzyme-catalyzed hydrolysis of echothiophate, a P–S bonded organophosphorus as monitored by spectrofluorimetry

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Enzyme-catalyzed hydrolysis of echothiophate, a P–S bonded organophosphorus (OP) model, was spectrofluorimetrically monitored, using Calbiochem Probe IV as the thiol reagent. OP hydrolases were: the G117H mutant of human butyrylcholinesterase capable of hydrolyzing OPs, and a multiple mutant of Brevundimonas diminuta phosphotriesterase, GG1, designed to hydrolyze a large spectrum of OPs at high rate, including V agents. Molecular modeling of interaction between Probe IV and OP hydrolases (G117H butyrylcholinesterase, GG1, wild types of Brevundimonas diminuta and Sulfolobus solfataricus phosphotriesterases, and human paraoxonase-1) was performed. The high sensitivity of the method allowed steady-state kinetic analysis of echothiophate hydrolysis by highly purified G117H butyrylcholinesterase concentration as low as 0.85 nM. Hydrolysis was michaelian with Km = 0.20 ± 0.03 mM and kcat = 5.4 ± 1.6 min−1. The GG1 phosphotriesterase hydrolyzed echothiophate with a high efficiency (Km = 2.6 ± 0.2 mM; kcat = 53,400 min−1). With a kcat/Km = (2.6 ± 1.6) × 107 M−1min−1, GG1 fulfills the required condition of potential catalytic bioscavengers. quantum mechanics/molecular mechanics (QM/MM) and molecular docking indicate that Probe IV does not interact significantly with the selected phosphotriesterases. Moreover, results on G117H mutant show that Probe IV does not inhibit butyrylcholinesterase. Therefore, Probe IV can be recommended for monitoring hydrolysis of P–S bonded OPs by thiol-free OP hydrolases

Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes

© 2016, Springer-Verlag Berlin Heidelberg.Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of acetylcholinesterase, a key enzyme in central and peripheral nervous systems. Numerous approaches, including chemical, physical, and biological decontamination, have been considered for developing decontamination methods against organophosphates (OPs). This work is an overview of both validated and emerging strategies for the protection against OP pollution with special attention to the use of decontaminating enzymes. Considerable efforts have been dedicated during the past decades to the development of efficient OP degrading biocatalysts. Among these, the promising biocatalyst SsoPox isolated from the archaeon Sulfolobus solfataricus is emphasized in the light of recently published results. This hyperthermostable enzyme appears to be particularly attractive for external decontamination purposes with regard to both its catalytic and stability properties