Recovery from spindle checkpoint-mediated arrest requires a novel Dnt1-dependent APC/C activation mechanism.

The activated spindle assembly checkpoint (SAC) potently inhibits the anaphase-promoting complex/cyclosome (APC/C) to ensure accurate chromosome segregation at anaphase. Early studies have recognized that the SAC should be silenced within minutes to enable rapid APC/C activation and synchronous segregation of chromosomes once all kinetochores are properly attached, but the underlying silencers are still being elucidated. Here, we report that the timely silencing of SAC in fission yeast requires dnt1+, which causes severe thiabendazole (TBZ) sensitivity and increased rate of lagging chromosomes when deleted. The absence of Dnt1 results in prolonged inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and attenuated protein levels of Slp1Cdc20, consequently slows the degradation of cyclin B and securin, and eventually delays anaphase entry in cells released from SAC activation. Interestingly, Dnt1 physically associates with APC/C upon SAC activation. We propose that this association may fend off excessive and prolonged MCC binding to APC/C and help to maintain Slp1Cdc20 stability. This may allow a subset of APC/C to retain activity, which ensures rapid anaphase onset and mitotic exit once SAC is inactivated. Therefore, our study uncovered a new player in dictating the timing and efficacy of APC/C activation, which is actively required for maintaining cell viability upon recovery from the inhibition of APC/C by spindle checkpoint.

Machine Learning-Assisted Eu(III)-Functionalized HOF-on-HOF Composite-Based Sensor Platform for Precise and Visual Identification of Multiple Pesticides.

Precise and rapid identification of pesticides is crucial to ensure a green environment, food safety, and human health. However, complex sample environments often hinder precise identification, especially for simultaneous differentiation of multiple pesticides. Herein, we first synthesize a Eu(III)-functionalized HOF-on-HOF composite (Eu@PFC-1@MA-TPA) and then utilize principal component analysis (PCA) and a machine learning (ML) algorithm to achieve simultaneous identification of the pesticides 2,6-dichloro-4-nitroaniline (DCN) and thiabendazole (TBZ) and their mixtures. Eu@PFC-1@MA-TPA displays high quantitative identification ability, which can distinguish single DCN and TBZ as low as 1 µM and their mixtures at 5 µM through PCA. In addition, the hydrogel film Eu@PFC-1@MA-TPA/AG is fabricated to monitor DCN and TBZ in drinking water, tap water, river water, and apple juice with high sensitivity. Furthermore, based on the obvious fluorescence color variance of pesticides, Eu@PFC-1@MA-TPA/AG achieves visual and in situ imaging detection of single DCN and TBZ and their mixtures. More importantly, we construct an intelligent artificial vision platform integrating Eu@PFC-1@MA-TPA/AG with a DenseNet algorithm, which can identify the concentrations and types of DCN and TBZ and their mixtures within 1 s with over 98% accuracy. This work develops a precise and rapid analysis method for simultaneous identification of multiple pesticides through combining a visualized fluorescence sensor and an ML algorithm.

O-nitrobenzyl Caged Molecule Enables Photo-controlled Release of Thiabendazole.

Pesticides are essential in agricultural development. Controlled-release pesticides have attracted great attentions. Base on a principle of spatiotemporal selectivity, we extended the photoremovable protective group (PRPG) into agrochemical agents to achieve controllable release of active ingredients. Herein, we obtained NP-TBZ by covalently linking o-nitrobenzyl (NP) with thiabendazole (TBZ). Compound NP-TBZ can be controlled to release TBZ in dependent to light. The irradiated and unirradiated NP-TBZ showed significant differences on fungicidal activities both in vitro and in vivo. In addition, the irradiated NP-TBZ displayed similar antifungal activities to the directly-used TBZ, indicating a factual applicability in controllable release of TBZ. Furthermore, we explored the action mode and microcosmic variations by SEM analysis, and demonstrated that the irradiated NP-TBZ retained a same action mode with TBZ against mycelia growth.

Rapid and specific detection of thiabendazole: enzymatic digestion-enabled fluorescent aptasensor.

Thiabendazole, a widely used broad-spectrum fungicide in agriculture, poses risks to human health. To monitor its presence in water, we propose a fluorescent aptasensor utilizing Escherichia coli exonuclease I (Exo I). The findings demonstrate a linear correlation between thiabendazole concentrations and digestion percentage, with a detection limit (LOD) exceeding 1 µM and a determination coefficient (R2) of 0.959. This aptamer-based fluorescence spectroscopy detection system holds promise for a rapid, specific, and sensitive analysis of thiabendazole in environmental waters and food matrices.

Analysis and experimental assessment of an optimized SERS substrate used to detect thiabendazole in apples with high sensitivity.

Pesticides that linger in the environment and ecosystems for an extended period can cause severe and dangerous health problems in humans. To detect pesticides in foods, the development of high-sensitivity and quick screening technologies was required. This research investigated the performance of Au@Ag NPs with varying thicknesses of the silver shell for detecting trace quantities of thiabendazole (TBZ) in apples using surface-enhanced Raman spectroscopy (SERS). The Au@Ag NPs were synthesized by coating 32 nm gold seeds with different thicknesses of silver shell ranging from 2.4 to 8.7 nm, achieved by adjusting the incorporation of AgNO3 and ascorbic acid. The optimized Au@Ag NPs with a 7.3 nm silver shell demonstrated outstanding SERS activity, high sensitivity, and a detection limit of 0.05 µg/mL for TBZ. The R2 values, representing the goodness of fit, were found to be 0.990 and 0.986 for standard and real TBZ samples, respectively, indicating a strong correlation between the measured signal and the TBZ concentration. The recovery analysis showed a reliable and accurate detection capability (96 to 105%), suggesting good reliability and accuracy of the SERS-based detection using the optimal Au@Ag NPs. Overall, this research highlights the potential of SERS with optimal Au@Ag NPs for rapid and effective monitoring of pesticides in the food industry.

Effect of cattle and horse feces storage methods on Nematode egg viability and sensitivity for egg hatch test.

The aim of the present study was to validate methods of stool sample conservation for the egg hatch test (EHT). This study involved the use of a bovine naturally infected predominantly by Cooperia spp. and one equine naturally infected predominantly by cyathostomins characterized as susceptible to benzimidazoles in the EHT. Fecal samples were submitted to three treatments: aerobic methods (anaerobic storage in plastic bottles, anaerobic storage in vacuum-sealed bags or aerobic storage in plastic bags), under two temperature conditions (room temperature and refrigeration) analyzed at four different assessment times (48, 72, 96 and 120 h). As the standard test, an assay was also performed within 3 h. The tests were performed in triplicate for each drug concentration and with three experimental repetitions at one-week intervals. Two criteria were used for the storage methods: hatchability in the negative control group and sensitivity of the eggs to thiabendazole, comparing the EC50 and 95% confidence interval for each treatment to those of the standard test and the other repetitions. Bovine samples can be stored for up to 96 h and refrigerated vacuum storage can be used, ensuring hatchability of the negative control and sensitivity of the eggs to thiabendazole. For equine samples, no forms of storage were indicated due to the variation among the repetitions and the reduction in the sensitivity of the eggs to thiabendazole, which could result in a false positive detection of resistance.

Exploring the Interactions between Plant Proanthocyanidins and Thiabendazole: Insights from Isothermal Titration Calorimetry.

Anthelmintic resistance in gastrointestinal nematodes produces substantial challenges to agriculture, and new strategies for nematode control in livestock animals are called for. Natural compounds, including tannins, with proven anthelmintic activity could be a functional option as structurally diverse complementary compounds to be used alongside commercial anthelmintics. However, the dual use of two anthelmintic components requires an understanding of the pharmacological effects of the combination, while information concerning the interactions between plant-based polyphenols and commercial anthelmintics is scarce. We studied the direct interactions of proanthocyanidins (PAs, syn. condensed tannins) and a commercial anthelmintic thiabendazole, as a model substance of benzimidazoles, by isothermal titration calorimetry (ITC). Our results show evidence of a direct interaction of an exothermic nature with observed enthalpy changes ranging from 0 to -30 kJ/mol. The strength of the interaction between PAs and thiabendazole is mediated by structural characteristics of the PAs with the strongest positive correlation originating from the presence of galloyl groups and the increased degree of polymerization.

Quantifying the effect of non-ionic surfactant alkylphenol ethoxylates on the persistence of thiabendazole on fresh produce surface.

BACKGROUND: Understanding the role of adjuvants in pesticide persistence is crucial to develop effective pesticide formulations and manage pesticide residues in fresh produce. This study investigated the impact of a commercial non-ionic surfactant product containing alkylphenol ethoxylates (APEOs) on the persistence of thiabendazole on apple and spinach surfaces against the 30 kg m-3 baking soda (sodium bicarbonate, NaHCO3 ) soaking, which was used to remove the active ingredient (AI) in the cuticular wax layer of fresh produce through alkaline hydrolysis. Surface-enhanced Raman scattering (SERS) mapping method was used to quantify the residue levels on fresh produce surfaces at different experimental scenarios. Four standard curves were established to quantify surface thiabendazole in the absence and presence of APEOs, on apple and spinach leaf surfaces, respectively. RESULTS: Overall, the result showed that APEOs enhanced the persistence of thiabendazole over time. After 3 days of exposure, APEOs increased thiabendazole surface residue against NaHCO3 hydrolysis on apple and spinach surfaces by 5.39% and 10.47%, respectively. CONCLUSION: The study suggests that APEOs led to more pesticide residues on fresh produce and greater difficulty in washing them off from the surfaces using baking soda, posing food safety concerns. © 2023 Society of Chemical Industry.

Field and Greenhouse Assessment of Seed Treatment Fungicides for Management of Sudden Death Syndrome and Yield Response of Soybean.

Seed treatments for the management of sudden death syndrome (SDS) caused by Fusarium virguliforme are available in the United States and Canada; however, side-by-side comparisons of these seed treatments are lacking. Sixteen field experiments were established in Illinois, Indiana, Iowa, Michigan, and Wisconsin, United States, and Ontario, Canada, in 2019 and 2020 to evaluate seed treatment combinations. Treatments included a nontreated check (NTC), fungicide and insecticide base seed treatments (base), fluopyram, base + fluopyram, base + saponin extracts from Chenopodium quinoa, base + fluopyram + heat-killed Burkholderia rinojenses, base + pydiflumetofen, base + thiabendazole + heat-killed B. rinojenses, and base + thiabendazole + C. quinoa extracts + heat-killed B. rinojenses. Treatments were tested on SDS moderately resistant and susceptible soybean cultivars at each location. Overall, NTC and base had the most root rot, most foliar disease index (FDX), and lowest yield. Base + fluopyram and base + pydiflumetofen were most effective for managing SDS. Moderately resistant cultivars reduced FDX in both years but visual root rot was greater on the moderately resistant than the susceptible cultivars in 2020. Yield response to cultivar was also inconsistent between the 2 years. In 2020, the susceptible cultivar provided significantly more yield than the moderately resistant cultivar. Treatment effect for root rot and FDX was similar in field and greenhouse evaluations. These results reinforce the need to include root rot evaluations in addition to foliar disease evaluations in the breeding process for resistance to F. virguliforme and highlights the importance of an integrated SDS management plan because not a single management tactic alone provides adequate control of the disease.

Review of Characteristics and Analytical Methods for Determination of Thiabendazole.

Thiabendazole (TBZ) is a fungicide and anthelmintic drug commonly found in food products. Due to its toxicity and potential carcinogenicity, its determination in various samples is important for public health. Different analytical methods can be used to determine the presence and concentration of TBZ in samples. Liquid chromatography (LC) and its subtypes, high-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UHPLC), are the most commonly used methods for TBZ determination representing 19%, 18%, and 18% of the described methods, respectively. Surface-enhanced Raman spectroscopy (SERS) and fluorimetry are two more methods widely used for TBZ determination, representing 13% and 12% of the described methods, respectively. In this review, a number of methods for TBZ determination are described, but due to their limitations, there is a high potential for the further improvement and development of each method in order to obtain a simple, precise, and accurate method that can be used for routine analysis.

Tannins Can Have Direct Interactions with Anthelmintics: Investigations by Isothermal Titration Calorimetry.

Plant tannins are known for their anthelmintic and antiparasitic activities and have been increasingly studied to battle the ever-growing problem of anthelmintic resistance. While tannins have been shown to exhibit these activities on their own, one approach would be to use them as complementary nutrients alongside commercial anthelmintics. So far, research on the interactions between tannins and anthelmintics is limited, and few studies have reported both synergistic and antagonistic effects depending on the type of tannin and the method used. These interactions could either strengthen or weaken the efficacy of commercial anthelmintics, especially if tannin-rich diets are combined with anthelmintics used as oral drenches. To study these interactions, a series of hydrolysable tannins (HTs) was selected, and their direct interactions with thiabendazole (TBZ) were evaluated by isothermal titration calorimetry (ITC), which allowed the detection of the exothermic interaction but also the roles and significances of different structural features of HTs in these interactions. Our results show that HTs can have a direct interaction with the benzimidazole anthelmintic TBZ and that the interaction is strengthened by increasing the number of free galloyl groups and the overall molecular flexibility of HTs.

Thiabendazole degradation by photo-NaOCl/Fe and photo-Fenton like processes, using copper slag as an iron catalyst, in spiked synthetic and real secondary wastewater treatment plant effluents.

Thiabendazole degradation (TBZD) in diferent types of water matrices was assessed by applying two Advanced Oxidation Processes, both using simulated solar light (SSL), copper slag (CS) as an iron based catalyst, and separately H2O2 or NaOCl as oxidants. First, optimum conditions for TBZD were evaluated in distilled water, TBZD = 90% at 60 min for CS-H2O2-SSL, and 92% of TBZD in a twelfth of the time by the system CS-NaOCl-SSL; minimum TBZ depletion variations were observed between the first and the fifth reuse test: 88 ± 2% for CS-H2O2-SSL (60 min) and 90 ± 1% for CS-NaOCl-SSL (5 min). Those conditions were tested using a synthetic (SE) and a real secondary effluent (RE) from a wastewater treatment plant. The CS-H2O2-SSL system achieved TBZD of 88 and 77% after 90 min for SE and RE, with kinetic constants of 0.024 and 0.016 min-1, respectively, whereas photo-NaOCl/Fe showed values of 0.365 and 0.385 min-1 for SE and RE, achieving a 94% TBZD removal in both types of water at 10 min. That might be related to the formation of Cl· and HO• during the photo-NaOCl/Fe process, highlighting that the CS-NaOCl-SSL is an attractive option that has great possibilities for scaling up by a better knowledge in real aqueous matrices.

Nutritional inter-dependencies and a carbazole-dioxygenase are key elements of a bacterial consortium relying on a Sphingomonas for the degradation of the fungicide thiabendazole.

Thiabendazole (TBZ), is a persistent fungicide/anthelminthic and a serious environmental threat. We previously enriched a TBZ-degrading bacterial consortium and provided first evidence for a Sphingomonas involvement in TBZ transformation. Here, using a multi-omic approach combined with DNA-stable isotope probing (SIP) we verified the key degrading role of Sphingomonas and identify potential microbial interactions governing consortium functioning. SIP and amplicon sequencing analysis of the heavy and light DNA fraction of cultures grown on 13 C-labelled versus 12 C-TBZ showed that 66% of the 13 C-labelled TBZ was assimilated by Sphingomonas. Metagenomic analysis retrieved 18 metagenome-assembled genomes with the dominant belonging to Sphingomonas, Sinobacteriaceae, Bradyrhizobium, Filimonas and Hydrogenophaga. Meta-transcriptomics/-proteomics and non-target mass spectrometry suggested TBZ transformation by Sphingomonas via initial cleavage by a carbazole dioxygenase (car) to thiazole-4-carboxamidine (terminal compound) and catechol or a cleaved benzyl ring derivative, further transformed through an ortho-cleavage (cat) pathway. Microbial co-occurrence and gene expression networks suggested strong interactions between Sphingomonas and a Hydrogenophaga. The latter activated its cobalamin biosynthetic pathway and Sphingomonas its cobalamin salvage pathway to satisfy its B12 auxotrophy. Our findings indicate microbial interactions aligning with the 'black queen hypothesis' where Sphingomonas (detoxifier, B12 recipient) and Hydrogenophaga (B12 producer, enjoying detoxification) act as both helpers and beneficiaries.

Thiabendazole Inhibits Glioblastoma Cell Proliferation and Invasion Targeting Mini-chromosome Maintenance Protein 2.

Thiabendazole (TBZ), approved by the US Food and Drug Administration (FDA) for human oral use, elicits a potential anticancer activity on cancer cells in vitro and in animal models. Here, we evaluated the efficacy of TBZ in the treatment of human glioblastoma multiforme (GBM). TBZ reduced the viability of GBM cells (P3, U251, LN229, A172, and U118MG) relative to controls in a dose- and time-dependent manner. However, normal human astrocytes (NHA) exhibited a greater IC50 than tumor cell lines and were thus more resistant to its cytotoxic effects. 5-Ethynyl-2'-deoxyuridine (EdU)-positive cells and the number of colonies formed were decreased in TBZ-treated cells (at 150 µM, P < 0.05 and at 150 µM, P < 0.001, respectively). This decrease in proliferation was associated with a G2/M arrest as assessed with flow cytometry, and the downregulation of G2/M check point proteins. In addition, TBZ suppressed GBM cell invasion. Analysis of RNA sequencing data comparing TBZ-treated cells with controls yielded a group of differentially expressed genes, the functions of which were associated with the cell cycle and DNA replication. The most significantly downregulated gene in TBZ-treated cells was mini-chromosome maintenance protein 2 (MCM2). SiRNA knockdown of MCM2 inhibited proliferation, causing a G2/M arrest in GBM cell lines and suppressed invasion. Taken together, our results demonstrated that TBZ inhibited proliferation and invasion in GBM cells through targeting of MCM2. SIGNIFICANCE STATEMENT: TBZ inhibits the proliferation and invasion of glioblastoma cells by downregulating the expression of MCM2. These results support the repurposing of TBZ as a possible therapeutic drug in the treatment of GBM.

Population replacement of benzimidazole-resistant Haemonchus contortus with susceptible strains: evidence of changes in the resistance status.

The spread of anthelmintic resistance (AR) in nematode populations threatens the viability of sheep production systems worldwide, and warrants the adoption of sensitive, practical, and standardized tests to detect AR. The aim of this study was to characterize the replacement of an Haemonchus contortus population resistant to benzimidazoles (BZDs) by a susceptible one, by means of both phenotypic and genotypic techniques. Phenotypic methods to assess BZD resistance included in vivo tests, such as the fecal egg count reduction test (FECRT), and in vitro tests, such as the egg hatch assay (EHA). Additionally, genotypification of polymorphisms associated with BZD resistance by sequencing a fragment of the isotype 1 ß-tubulin gene was carried out. The initial, BZD-resistant population (initial Balcarce population) exhibited an egg count reduction (ECR) of 59.3%. Following refugium replacement, the final population (final Balcarce population) exhibited an ECR of 95.2%. For the initial Balcarce population, the median effective dose (ED50) for the EHA was 0.607 µg thiabendazole (TBZ)/mL, with a rate of eclosion at a discriminating dose (EDD) of 0.1 µg TBZ/mL of 76.73%. For the final Balcarce population, ED50 was 0.02 µg TBZ/mL, and EDD was 1.97%. In the initial population, 93% of the analyzed individuals exhibited genotypic combinations associated with BZD resistance (53% Phe/Phe167-Tyr/Tyr200, 37% Phe/Tyr167-Phe/Tyr200, and 3% Phe/Tyr167-Glu/Leu198). Conversely, no combination associated with resistance was found in individuals from the final population. All of the tests were useful for detecting AR to BZDs. The results from the genetic and phenotypical studies were consistent, and the resulting information greatly aided in interpreting the outcomes of the population replacement and the potential impact of this strategy on management of AR.

Comparative Performance of Fungicides and Biocontrol Products in the Management of Fusarium Wilt of Blackberry.

Fusarium wilt of blackberry (FWB) is an emerging disease caused by a Fusarium oxysporum species complex. More than 3,000 ha of blackberry (Rubus spp.) crops have been lost in Mexico since 2011. The objectives of this research were: to evaluate the sensitivity of pathogenic F. oxysporum isolates recovered from symptomatic blackberry plants to fungicides with different modes of action; to assess the potential of these fungicides and plant resistance inducers against FWB in the greenhouse; and to determine the effects of commercial biofungicides and two indigenous strains of Trichoderma spp. on the incidence of FWB. The EC50 values of the fungicides prochloraz, thiabendazole, azoxystrobin, thiophanate-methyl, difenoconazole, triflumizole, and potassium phosphite for six pathogenic F. oxysporum isolates were determined. In a separate experiment, the fungicides acibenzolar-s-methyl (ASM), potassium phosphite, and commercial biofungicides, as well as two soil microbial inoculants and two indigenous Trichoderma strains, were tested for protection against wilt development in blackberry plants in the greenhouse. Prochloraz showed an average sensitivity for EC50 of 0.01 µg ml-1 for the tested F. oxysporum isolates, followed by difenoconazole and thiabendazole. Prochloraz and ASM proved to be the most effective treatments in the greenhouse. In contrast, potassium phosphite was ineffective in both the in vitro and in vivo experiments. The soil bioinoculants MicroSoil, Baktillis, T. koningiopsis, and T. asperellum significantly reduced the incidence of disease in the greenhouse. These results provide evidence for the potential of the various tools as useful components of integrated FWB management in the field.

A New, MWCNT-Based, Solid-State Thiabendazole-Selective Sensor.

Direct potentiometric measurements using solid-state sensors have a great potential for thiabendazole (TBZ) determination, considering simplicity, accuracy, and low cost. Modifying the sensing material of the sensor with multi-walled carbon nanotubes (MWCNTs) leads to improved analytical properties of the sensor. In this study, a new potentiometric solid-state sensor for TBZ determination, based on MWCNTs modified with a sulfate group, and TBZ ion as sensing material was developed. The sensor exhibited a Nernstian response for TBZ (60.4 mV/decade of activity) in a working range between 8.6 × 10-7 and 1.0 × 10-3 M. The detection limit for TBZ was 6.2 × 10-7 M. The response time of the sensor for TBZ was 8 s, and its signal drift was only 1.7 mV/h. The new sensor is applicable for direct potentiometric determination of TBZ in complex real samples, such as fruit peel. The accuracy of TBZ determination is confirmed using the standard addition method.

Machine Learning-Assisted Synchronous Fluorescence Sensing Approach for Rapid and Simultaneous Quantification of Thiabendazole and Fuberidazole in Red Wine.

Rapid analysis of components in complex matrices has always been a major challenge in constructing sensing methods, especially concerning time and cost. The detection of pesticide residues is an important task in food safety monitoring, which needs efficient methods. Here, we constructed a machine learning-assisted synchronous fluorescence sensing approach for the rapid and simultaneous quantitative detection of two important benzimidazole pesticides, thiabendazole (TBZ) and fuberidazole (FBZ), in red wine. First, fluorescence spectra data were collected using a second derivative constant-energy synchronous fluorescence sensor. Next, we established a prediction model through the machine learning approach. With this approach, the recovery rate of TBZ and FBZ detection of pesticide residues in red wine was 101% ± 5% and 101% ± 15%, respectively, without resorting complicated pretreatment procedures. This work provides a new way for the combination of machine learning and fluorescence techniques to solve the complexity in multi-component analysis in practical applications.

Deciphering Molecular Determinants Underlying Penicillium digitatum's Response to Biological and Chemical Antifungal Agents by Tandem Mass Tag (TMT)-Based High-Resolution LC-MS/MS.

Penicillium digitatum is a widespread pathogen responsible for the postharvest decay of citrus, one of the most economically important crops worldwide. Currently, chemical fungicides are still the main strategy to control the green mould disease caused by the fungus. However, the increasing selection and proliferation of fungicide-resistant strains require more efforts to explore new alternatives acting via new or unexplored mechanisms for postharvest disease management. To date, several non-chemical compounds have been investigated for the control of fungal pathogens. In this scenario, understanding the molecular determinants underlying P. digitatum's response to biological and chemical antifungals may help in the development of safer and more effective non-chemical control methods. In this work, a proteomic approach based on isobaric labelling and a nanoLC tandem mass spectrometry approach was used to investigate molecular changes associated with P. digitatum's response to treatments with α-sarcin and beetin 27 (BE27), two proteins endowed with antifungal activity. The outcomes of treatments with these biological agents were then compared with those triggered by the commonly used chemical fungicide thiabendazole (TBZ). Our results showed that differentially expressed proteins mainly include cell wall-degrading enzymes, proteins involved in stress response, antioxidant and detoxification mechanisms and metabolic processes such as thiamine biosynthesis. Interestingly, specific modulations in response to protein toxins treatments were observed for a subset of proteins. Deciphering the inhibitory mechanisms of biofungicides and chemical compounds, together with understanding their effects on the fungal physiology, will provide a new direction for improving the efficacy of novel antifungal formulations and developing new control strategies.

Infection Dynamics of ATG8 in Leishmania: Balancing Autophagy for Therapeutics.

In many regions of the world, Leishmaniasis is a cause of substantial mortality and ailment. Due to impediment in available treatment, development of novel and effective treatments is indispensable. Significance of autophagy has been accentuated in infectious disease as well as in Leishmaniasis, and it is having capability to be manifested as a therapeutic target. By evincing autophagy as a novel therapeutic regime, this study emphasized on the critical role of ATG4.1-ATG8 and ATG5-ATG12 complexes in Leishmania species. The objective here was to identify ATG8 as a potential therapeutic target in Leishmania. R71T, P56E, R18P are the significant mutations which shows detrimental effect on ATG8 while Arg276, Arg73, Cys75 of ATG4.1 and Val88, Pro89, Glu116, Asn117, and Gly120 are interacting residues of ATG8. Along with this, we also bring into spotlight an enticing role of Thiabendazole derivatives that interferes with the survival mechanisms by targeting ATG8. Further, the study claims that thiabendazole can be a potential drug candidate to target autophagy process in the infectious disease Leishmaniasis.