fmicb-11-00868 May 15, 2020 Time: 17:30 # 1 REVIEW published: 19 May 2020 doi: 10.3389/fmicb.2020.00868 Insights Into the Microbial Degradation and Biochemical Mechanisms of Neonicotinoids Shimei Pang1,2, Ziqiu Lin1,2, Wenping Zhang1,2, Sandhya Mishra1,2, Pankaj Bhatt1,2 and Shaohua Chen1,2* 1 State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China, 2 Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China Neonicotinoids are derivatives of synthetic nicotinoids with better insecticidal capabilities, including imidacloprid, nitenpyram, acetamiprid, thiacloprid, thiamethoxam, Edited by: clothianidin, and dinotefuran. These are mainly used to control harmful insects and pests Guining Lu, to protect crops. Their main targets are nicotinic acetylcholine receptors. In the past two South China University of Technology, decades, the environmental residues of neonicotinoids have enormously increased due China to large-scale applications. More and more neonicotinoids remain in the environment Reviewed by: Xiaomei Su, and pose severe toxicity to humans and animals. An increase in toxicological and Zhejiang Normal University, China hazardous pollution due to the introduction of neonicotinoids into the environment Santosh Kr. Karn, Sardar Bhagwan Singh Post causes problems; thus, the systematic remediation of neonicotinoids is essential Graduate Institute of Biomedical and in demand. Various technologies have been developed to remove insecticidal Sciences & Research, India residues from soil and water environments. Compared with non-bioremediation *Correspondence: methods, bioremediation is a cost-effective and eco-friendly approach for the treatment Shaohua Chen [email protected] of pesticide-polluted environments. Certain neonicotinoid-degrading microorganisms, including Bacillus, Mycobacterium, Pseudoxanthomonas, Rhizobium, Rhodococcus, Specialty section: Actinomycetes, and Stenotrophomonas, have been isolated and characterized. These This article was submitted to Microbiotechnology, microbes can degrade neonicotinoids under laboratory and field conditions. The a section of the journal microbial degradation pathways of neonicotinoids and the fate of several metabolites Frontiers in Microbiology have been investigated in the literature. In addition, the neonicotinoid-degrading Received: 13 January 2020 Accepted: 14 April 2020 enzymes and the correlated genes in organisms have been explored. However, few Published: 19 May 2020 reviews have focused on the neonicotinoid-degrading microorganisms along with Citation: metabolic pathways and degradation mechanisms. Therefore, this review aimed to Pang S, Lin Z, Zhang W, summarize the microbial degradation and biochemical mechanisms of neonicotinoids. Mishra S, Bhatt P and Chen S (2020) Insights Into the Microbial The potentials of neonicotinoid-degrading microbes for the bioremediation of Degradation and Biochemical contaminated sites were also discussed. Mechanisms of Neonicotinoids. Front. Microbiol. 11:868. Keywords: neonicotinoids, toxicity, microbial degradation, metabolic pathways, bioremediation, molecular doi: 10.3389/fmicb.2020.00868 mechanisms Frontiers in Microbiology| www.frontiersin.org 1 May 2020| Volume 11| Article 868 fmicb-11-00868 May 15, 2020 Time: 17:30 # 2 Pang et al. Biodegradation of Neonicotinoids INTRODUCTION a dangerous threat to humans and ecosystems (Casida, 2017; Humann-Guilleminot et al., 2019). These insecticides are The increasing global demand for food and productive crops considered a key factor in diminishing pollinating insects, has facilitated tremendous growth of the pesticide sector. especially honeybees (Friedli et al., 2020). Neonicotinoids can Neonicotinoid insecticides have been widely used for the be adhered easily to the surface of plants, animals, and human protection of crops from a variety of insects and pests, to enhance beings, and do not degrade easily into the environment (Hladik production (Simon-Delso et al., 2015). These crops include rice, et al., 2018). Due to the toxic and hazardous effects to bees, wheat, maize, soybean, cotton, sugar beet, apple, potato, etc. the outdoor use of neonicotinoids is banned in European Neonicotinoid insecticides are developed and synthesized based Union member states. on nicotine structure research with better insecticidal capabilities Usually, both biotic and abiotic factors, including chemicals, (Humann-Guilleminot et al., 2019). Neonicotinoids are a kind sunlight, and microbial agents, promote the degradation of of neuroactive insecticide. Their insecticidal mechanism involves native and foreign organisms in the soil (Chen et al., 2015; the action of nicotine acetyl bile on the postsynaptic membrane Birolli et al., 2018; Yang et al., 2018; Zhan et al., 2018a; Bhatt of insect nicotinic acetylcholine receptors (nAChRs) whereas the et al., 2020c; Zhang et al., 2020). Microbial degradation is often surrounding nerves induce excitation leading to paralysis and used to transform synthetic chemicals into inorganic products death (Zhang et al., 2018). There is no cross-resistance to the (Chen et al., 2011, 2013; Arora et al., 2017; Cycoñ et al., traditional long-acting insecticide classes due to the user mode 2017; Huang et al., 2019; Feng et al., 2020a). Uncontrollable of action (MoA). Therefore, neonicotinoids replace those of photocatalytic conditions are the major disadvantage of non- organochlorine, organophosphorus, chlorinated hydrocarbons, biological degradation and thus microbial degradation emerges carbamate, pyrethroid insecticides, and several other chemical as a better alternative (Zhang et al., 2018). It is usually insufficient categories (Jeschke and Nauen, 2008). In the mid-1980s, Bayer for analytical procedures to report the concentrations as most contributed to imidacloprid (1-[(6-chloro-3-pyridinyl)-methyl]- countries generally lack the environmental monitoring data N–nitro-2-imidazolidinimine), which was the first neonicotinoid systematically for neonicotinoids. insecticide, and this captured one of the highest shares in Individual neonicotinoid concentrations from the water the global pesticide market (Peter et al., 2010). Worldwide, monitoring literature demonstrated average surface water neonicotinoids accounted for approximately one-quarter of concentrations of 0.13 mg·L−1 (n = 19 studies) and a peak the pesticide market, and their annual production was about surface water concentration of 0.63 mg·L−1 (n = 27 studies) 600,000 tons (Simon-Delso et al., 2015). The broad-spectrum (Christy et al., 2015). The fate of neonicotinoid insecticides characteristics and high insecticidal activity of imidacloprid in the soil environment is greatly decided by the microbial led to the development of a series of nicotinic insecticides, metabolisms. However, bacteria with a complete set of genes including thiamethoxam, clothianidin, dinotefuran, acetamiprid, required for complete mineralization have not been found thiacloprid, and nitenpyram. yet. Soil microbial degradation processes of imidacloprid, Neonicotinoids include three main compounds: acetamiprid, and thiacloprid have been understood; however, little has been reported regarding the microbial degradation 1 Chloropyridinyl compounds (imidacloprid, nitenpyram, of clothianidin, dinotefuran, thiamethoxam, and nitenpyram acetamiprid, and thiacloprid), (Mulligan et al., 2016). 2 Chlorothiazolyl compounds (thiamethoxam and The microbial degradation of neonicotinoids is considered clothianidin), and to be the most efficient and environmentally friendly in situ 3 Tetrahydrofuran compounds (dinotefuran) (Table 1). repair pathway (Hamada et al., 2019). The use of potential and degradative microorganisms, which can grow and survive Neonicotinoids are commonly used for seed treatment, soil under high-stress concentrations of insecticides, offers a possible wetting, and foliage sprays to protect crop seedlings from leaf- opportunity for the remediation of toxic pollutants and eating insects (Hussain et al., 2016). Neonicotinoids are water- hazardous wastes from contaminated environments (Chen et al., soluble at concentrations of 184–590.0 mg·L−1 at 20◦C and 2014; Rana et al., 2015; Xiao et al., 2015; Zhan et al., 2018b; pH 7. Therefore, neonicotinoids are absorbed and circulated Bhatt et al., 2020a). throughout the plant system to protect against insects (Ellis et al., A variety of neonicotinoid-degrading microorganisms have 2017). Neonicotinoids bind and activate the postsynaptic nAChR been isolated and identified. These microbes include Bacillus, of insects, which causes muscle tremors and cell fatigue. The Mycobacterium, Pseudoxanthomonas, Rhizobium, Rhodococcus, effect of neonicotinoids is significantly stronger on invertebrates Actinomycetes, and Stenotrophomonas (Dankyi et al., 2018; Zhang than vertebrates as vertebrates have more nAChRs (Taillebois et al., 2018; Hamada et al., 2019). The bioremediation potential et al., 2018; Zaworra et al., 2018). Neonicotinoids are efficient of neonicotinoid-contaminated water/soil environments using insecticides with low toxicity but their long-term usage has several different microbes has been investigated. However, generated extensive environmental problems (Mariusz et al., the detailed knowledge about specific degradative enzymes 2013). These compounds not only affect the growth of plants and genes still needs