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Protein-Based Bioscavengers of Organophosphorus Nerve Agents
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Moshe Goldsmith, Yacov Ashani, Tamara. C. Otto, C. Linn Cadieux, David. S. Riddle
A number of homologs of PTE, termed PTE-like lactonases (PLLs) (Afriat et al., 2006), have been isolated from extremophile bacteria such as Sulfolobus solfataricus (SsoPox) (Merone et al., 2005), S. acidocaldarius (SacPox) (Porzio et al., 2007), S. islandicus (SisLac) (Hiblot et al., 2012b), Vulcanisaeta moutnovskia (VmutPLL) (Hiblot et al., 2013), Deinococcus radiodurans (Dr0930) (Xiang et al., 2009), and Geobacillus stearothermophilus (GsP) (Hawwa et al., 2009). Since all of them exhibit different degrees of OP hydrolysis (e.g., Elias et al., 2008; Hiblot et al., 2012a,b; Kallnik et al., 2014), and since they all exhibit enhanced stabilities relative to proteins from mesophilic bacteria (e.g., PTE and PON1), they were proposed to serve as candidates for the development of catalytic scavengers for bioremediation and surface decontamination purposes (Jacquet et al., 2016). However, as with catalytic bioscavengers developed for medical countermeasures, the catalytic efficiency of these enzymes with OPNAs needs to be improved to make their use applicable and their production economically feasible. Using directed evolution and selection for paraoxon hydrolysis, the catalytic efficiencies of SsoPox were improved by 2210-, 163-, 58-, and 16- fold with methyl-parathion, malathion, ethyl-paraoxon, and methyl-paraoxon, respectively, in a single variant (Jacquet et al., 2017). The activity of this variant with OPNAs is expected to be improved, as previous work has shown that the turnover rate of SsoPox with the toxic isomer of cyclosarin was improved fourfold following selection for improved paraoxon hydrolysis(Merone et al., 2010). Thus, while the catalytic efficiency goal for effective surface decontamination and bioremediation using a catalytic bioscavenger has not yet been determined, it seems that there are a number of promising candidates for the development of such bioscavengers.
Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose
Published in International Journal of Radiation Biology, 2018
Jagdish Gopal Paithankar, Shamprasad Varija Raghu, Rajashekhar K. Patil
Among living organisms, different sensitivities towards IR were reported. Some organisms were found sensitive to few Gray (Gy) dose of IR and some could withstand up to thousands of Gy (Harrison and Anderson 1996; Bakri et al. 2005). Some organisms were even reported to help other organisms to withstand against IR stress; microbial cells were reported to assist during chronic stress of IR (Shuryak et al. 2017). Along with prokaryotic microorganisms, single cell eukaryote; yeast was also reported to have high radiation tolerance (Tkavc et al. 2018). Similar to other insects, adults of the fruit fly Drosophila melanogaster (D. melanogaster) were reported to have the lethal dose to kill 50% population (LD50) above 1200 Gy (Parashar et al. 2008; Paithankar et al. 2017), whereas humans reported to have the LD50 of 3 Gy (Harrison and Anderson 1996). Recently, we reported that different life stages of D. melanogaster have different levels of radiation resistance and most of its life stages withstand at doses more than 1000 Gy (Paithankar et al. 2017). It is believed that the property of radiation resistance is by the virtue of specialized mechanisms. There is a combination of mechanisms suggested for radiation resistance in a microbe Deinococcus radiodurans (Daly 2009; Krisko and Radman 2013) and over a period of time certain hypothesis came elucidating the property of radiation resistance, such as (a) efficient antioxidant mechanisms, (b) prevention of DNA damage, (c) modified DNA repair system, (d) improved stress responses, (e) lack of holokinetic chromosomes, and (f) resistance against radiation-induced apoptosis (Chandna 2010). For decades, it was tacitly assumed that DNA damage is the prime cause of radiation sensitivity. Recently, it has been reported that protein damage is in the cardinal position to determine sensitivity to IR (Krisko and Radman 2013). Proteins can undergo several kinds of oxidative modifications, the extent of modification by carbonylation was reported several times greater; therefore, protein carbonyl (PC) have been widely used as a marker in diseases, oxidative stress, and ageing (Stadtman and Levine 2006).