Arsenic as Next Global Threat? Role of Biotechnological Approaches

Arsenicosis is about potent toxicity and carcinogenic effect of arsenic but sometime it had been used for medicinal purpose in old times also. Nowadays it has been emerging as a new threat for human community at large because of recent report of arsenic mobilization in food chain. Study reveals presence of high arsenic concentration not only in drinking water but also in in many food crops, meat and other consumables. Many part of world is facing acute crisis such as Bangladesh, china India, and many more countries as depicted in Figure 1 and in more than 70 countries, peoples are severely effected by groundwater arsenic contamination and need urgent interventions. Bangladesh has been declared as one of the worst natural calamities where rural and urban communities are facing severe consequences in form of skin cancer such as keratosis and melanosis. In India, Malwa, Punjab, has been declared as Cancer belt, where intense sign of cancer has been reported in skin and other vital organs.

glycoporins Metalloid arsenic has several structural form (Table 1), and can combine with many metals such as iron and molybdenum but Arsenic III (inorganic form) is most toxic form and is accumulating and entering in food chain constantly, escalating arsenic mobility issue more than calculated one. Further environmental condition such as pH, floods (redox condition), are conducive in high mobility and interconversions of arsenic getting complexed with many other compounds, favouring their easy transport in rice and other seeds via multiple transporters e.g., aquaglyceroporins in both plant and animals [1].
Marine organism had exceeding high levels of arsenic accumulation in non-toxic organic form arsenobetain, while rice is reported to have exceeding levels of inorganic arsenic (III). Arsenate As (V) is nontoxic form but it becomes toxic when arsenic (V) combines with phosphate or iron oxide and thus inhibits phosphorylation processes after entering the cells. Arsenate As (III) causes deactivation of enzyme due to its high affinity towards thiol groups. In addition, inorganic arsenic enters the cell via the hexose transporter, phosphate transporter systems (PTS) or aqua-glycoporins, while rice and other plants had different transporter. Arsenic reductase coded by Ars or Arr operon are helpful in conversion of arsenite to arsenate in both prokaryotes and eukaryotes and some microbes has ability to pump out exceeding arsenite after detoxification. Arsenic detoxification in multicellular organisms is based on methylation pattern and further oxidation makes arsenic less toxic basically arsenic (III) is converted into arsenic (V) which is excreted in urine of human being. However, since human has limited capacity of conversion, therefore high accumulation causes various malfunctioning such as keratosis and melanosis.
Microbial action is thought to provoke high mobilisation of arsenic via arsenic reductases after solubilisation of arsenic complex due to chelation. Methylation is believed to be one of the important mechanisms present in all organism including many microbes such as bacteria, fungi, and even higher plants, other organisms that converts them back in non-toxic form. Mostly, alternative oxidation and reduction is the basis of conversion of one form of arsenic into other. Even though arsenite is more toxic than arsenate, this transformation is essential, since only arsenite can be methylated. Arsenite is methylated to methylarsonate, which is reduced to methylarsonite and further to dimethylarsinate and to dimethylarsinous acid [2].
Arsenic contamination in non-effected area is of great concern today and spreading via food chain. Old strategies for arsenic mitigation were not only costly, but also results in large amount of sludge production, which was difficult to detoxify in one-step. Many worker believes that comprehensive multistep approaches towards escalating problems is essential in mitigation of arsenic means both chemical as well as biotechnological approaches can work in synchronous matter. Therefore, alternative techniques may be helpful in order to prevent the entry of arsenic in the food chain. One of the most relevant strategies seems to be the application of arsenic resistance microbes equipped with both uptake and detoxification machinery for sequestration and introduction of novel genes into food crops. Many endophytes isolated from hyper accumulator's plants have role in mobilization of arsenic. Metagenomics approaches seems to be plausible in finding potential microbes in order to enhanced bioremediation capability of arsenic on the basis of presence of clusters of genes and gene networks present for As sequestration and metabolism [3]. Many hyper accumulators are known to adsorb more than 95% of the arsenic from the soil as evident by the fern (P. vittata) [4]. Unfortunately, the plant P. vittata grows well only in warm, humid environments with mild winters, therefore they cannot grow everywhere in every environment. Therefore, some scientist are making efforts to increase the ability of plants to pump out arsenic from soil via creating GMO plants which have gene for both mobility and sequestration of arsenic and beside this some more gene required like metal chelator, metallothionein (MT), metal transporter, and phytochelatin (PC) genes [5]. Dhanker and colleagues constructed Arabidopsis plants, where, γ -ECS gene related to mobility was introduced and the arsenate reductase C (ArsC) gene to control the sequestration of arsenic [3,6,7]. Compared to other techniques, biomass based techniques are more useful. Some research on endophytes related to bioremediation and use of arbuscular mycorrhizas (AMs) are also involve absorption of arsenic. Mycorrhizas are vital for some plants since these are fungi associate with plant roots, so an important tools in increasing uptake of nutrients, especially phosphorus. AM fungi may be helpful in increased arsenic uptake along with hyper accumulating fern P. vittata The arsenic translocation factor (TF) was reported to increase in AM-inoculated plants as compared with Uninoculated plants, for example in Glomus mosseae-inoculated plants TF factor was 730 as compared to 50 as compared to control plants. Since arsenate shares structural similarity with phosphate and thus many hyper accumulator species such as P. vittata absorbs arsenate via phosphate transport system (PTS) or with other metal transporter system [8]. Secretion of various chemical chelators also increases rapid uptake of arsenic but mostly plants lacks adequate system to adsorb arsenic rapidly.
Some edible microbes such as Lactic acid bacteria has various special characteristic features such as secretion of antibacterial substances (bacteriocins) presence of arsenic reductase (Ars C). Lactobacillus lactis reported to contains GSH which protects bacterium under extreme acidic conditions [9,10]. Use of LAB is limited in adsorption since they requires surface modifications for perfect adsorption of arsenic. There are presence of many secondary transporter Ars A, Ars B, Ars C operon that makes them arsenic resistant bacteria but they fail to adsorb Cobalt, Copper, Nickel, and Iron metals [9]. Bacillus adsorb wide range of metals such as mercury, lead and cadmium, while Staphylococcus, E. coli, Lactobacillus are arsenic resistance [11,12]. Known Lactobacillus species for arsenic are Lactobacillus acidophilus, L. Crispatus, while Pseudomonas proteda, Bacillus subtilis, L. rhamnosus, Bifido bacterium and Lactobacillus plantarum [9,13,14]. Both facultative aerobic and anaerobic e.g., bacillus, clostridium reported to remove metal ions rapidly [15][16][17]. Presence of metal resistance shows microbial capability to survive in the environment, which can be harnessed as an effective mitigation strategy for arsenic [11,18,19]. Arsenite III is mostly dominating in anoxic water such as floods and via root uptake enters in seedlings. DARP (Dissimilatory Arsenate-respiring prokaryotes) [20] is associated with arsenic reduction via electrons exchange via release of chelators such as lactate, acetate and formate. These microbes utilizes 'arr' biomarkers [21] and thrive well in deep sea, deep well and lake or contaminated aquifers [22].
For arsenic detoxification arsenate and arsenite operon is present in both the gram positive as well as gram negative bacteria. arr operon is related to arsenic reductase present in many microbes such as Shewanella, bacillus some organism like E. coli, Staphylococcus, Bacillus, Acidithiobacillus, Pseudomonas, had well characterised Ars operon linked with As(V) detoxification where. In these organisms, As (V) is converted to As (III) via arsenic reductase, which triggers ars operon. Actually, these operons are linked with efflux and transporter protein, as a result arsenic V enters via phosphate transporter protein while Ars III is efflux after activation of Ars operon [16]. Endophytes are part of plant system and thus may help in mobilisation of nutrients and arsenic along with Arsenic V which is analogous to phosphate while some rhizospheric endophytes stops mobilization of arsenic metals. There is more bioavailability of arsenic or deposits of arsenic. Rather than

Arsenic form Sources Comments References
Sodium Arsenate Pesticides and wood [27] DMA (also known as cacodylic acid) have been widely used as pesticides and herbicides Preservatives [28,29] Arsenopyrite Rocks, Soils, Minerals, mines [15,49] Ground water Arsenite, arsenate [30] Arsenobetaine, Arsenocholine, tetramethylarsonium salts Organic forms (methyl and dimethyl arsenic compounds) [31] Arsenosugars Coal-fired power generation [32] Plants, burning vegetation and also due to eruption of volcano [33] Fe-reducing bacteria are linked to the mobilization of As in aquifer of the river delta in Bangladesh.

Arsenobetaine
Marine animal [35] [(CH 3 ) 3 As+CH 2 COOH] dimethylarsinic acid Soil [36] arsenobetain MMA, DMA, TMAO Plants [37][38][39] Arsenic III, DMA, MMA, MA As-cysteine, As 2 S 3 and As 2 O 5 [40,41] arsenate, arsenite, MMA and DMA Soil, rice [42] Asbet, Aschol, arsenosugars, arsenolipids Sea foods No harm by intake [43,44] As(III), DMA,MMA, As(V) Urine wine club soda [45] Legume-rhizobium Sunflower  single microbes to act for decontamination groups of microbes (called as Biome) activates for maintaining balance between toxic metals. Recently, addition of SiO, or iron oxide (Fe 2 O 3 or Fe 3 O 4 ) nanoparticle in soil resulted in increasing growth of specific micro-organism specially anaerobic arsenic reducing microbes, which resulted in enhanced uptake, via rapid mobilization and precipitation of arsenic in presence of sodium acetate. This reduction strategies is actually depends on presence of specific operon, such as Arr operon. Treatment of NPs with sodium acetate increases precipitation of arsenic due to electron donating capacity [23,24]. In assisting microbial bioremediation plants may have vital absorptive role in aim to survival strategies, Bayer et al. [25,26] has recently studied a detail mechanism of interaction between plant and microbes via metagenomics study [48]. In conclusion, more research effort is required in pilot scale study which may represent a confirmative mitigation of arsenic from food chain [49,50].