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Trichomoniasis in humans, caused by the protozoal parasite Trichomonas vaginalis, is the most common non-viral sexually transmitted disease, while Tritrichomonas foetus causes trichomonosis, an infection of the gastrointestinal tract and diarrhea in farm animals and domesticated cats. As part of an effort to determine the inhibitory effects of plant-based extracts and pure compounds, seven commercially available cherry tomato varieties were hand-peeled, freeze-dried, and pounded into powders. The anti-trichomonad inhibitory activities of these peel powders at 0.02% concentration determined using an in vitro cell assay varied widely from 0.0% to 66.7% against T. vaginalis G3 (human); from 0.9% to 66.8% for T. foetus C1 (feline); and from 0.0% to 81.3% for T. foetus D1 (bovine). The organic Solanum lycopersicum var. cerasiforme (D) peels were the most active against all three trichomonads, inhibiting 52.2% (G3), 66.8% (C1), and 81.3% (D1). Additional assays showed that none of the powders inhibited the growth of foodborne pathogenic bacteria, pathogenic fungi, or non-pathogenic lactobacilli. Tomato peel and pomace powders with high content of described biologically active compounds could serve as functional food and feed additives that might help overcome adverse effects of wide-ranging diseases and complement the treatment of parasites with the anti-trichomonad drug metronidazole.
Mendel Friedman; Christina Tam; Jong Kim; Sydney Escobar; Steven Gong; Max Liu; Xuan Mao; Cindy Do; Irene Kuang; Kelvin Boateng; Janica Ha; Megan Tran; Srimanth Alluri; Tam Le; Ryan Leong; Luisa Cheng; Kirkwood Land. Anti-Parasitic Activity of Cherry Tomato Peel Powders. Foods 2021, 10, 230 .
AMA StyleMendel Friedman, Christina Tam, Jong Kim, Sydney Escobar, Steven Gong, Max Liu, Xuan Mao, Cindy Do, Irene Kuang, Kelvin Boateng, Janica Ha, Megan Tran, Srimanth Alluri, Tam Le, Ryan Leong, Luisa Cheng, Kirkwood Land. Anti-Parasitic Activity of Cherry Tomato Peel Powders. Foods. 2021; 10 (2):230.
Chicago/Turabian StyleMendel Friedman; Christina Tam; Jong Kim; Sydney Escobar; Steven Gong; Max Liu; Xuan Mao; Cindy Do; Irene Kuang; Kelvin Boateng; Janica Ha; Megan Tran; Srimanth Alluri; Tam Le; Ryan Leong; Luisa Cheng; Kirkwood Land. 2021. "Anti-Parasitic Activity of Cherry Tomato Peel Powders." Foods 10, no. 2: 230.
Control of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs could also trigger human cytotoxicity associated with the kidneys and liver, including the generation of reactive oxygen species. Moreover, increased incidences of fungal resistance to the classes of azoles, such as fluconazole, itraconazole, voriconazole, or posaconazole, or echinocandins, including caspofungin, anidulafungin, or micafungin, have been documented. Of note, certain azole fungicides such as propiconazole or tebuconazole that are applied to agricultural fields have the same mechanism of antifungal action as clinical azole drugs. Such long-term application of azole fungicides to crop fields provides environmental selection pressure for the emergence of pan-azole-resistant fungal strains such as Aspergillus fumigatus having TR34/L98H mutations, specifically, a 34 bp insertion into the cytochrome P450 51A (CYP51A) gene promoter region and a leucine-to-histidine substitution at codon 98 of CYP51A. Altogether, the emerging resistance of pathogens to currently available antifungal drugs and insufficiency in the discovery of new therapeutics engender the urgent need for the development of new antifungals and/or alternative therapies for effective control of fungal pathogens. We discuss the current needs for the discovery of new clinical antifungal drugs and the recent drug repurposing endeavors as alternative methods for fungal pathogen control.
Jong H. Kim; Luisa W. Cheng; Kathleen L. Chan; Christina C. Tam; Noreen Mahoney; Mendel Friedman; Mikhail Martchenko Shilman; Kirkwood M. Land. Antifungal Drug Repurposing. Antibiotics 2020, 9, 812 .
AMA StyleJong H. Kim, Luisa W. Cheng, Kathleen L. Chan, Christina C. Tam, Noreen Mahoney, Mendel Friedman, Mikhail Martchenko Shilman, Kirkwood M. Land. Antifungal Drug Repurposing. Antibiotics. 2020; 9 (11):812.
Chicago/Turabian StyleJong H. Kim; Luisa W. Cheng; Kathleen L. Chan; Christina C. Tam; Noreen Mahoney; Mendel Friedman; Mikhail Martchenko Shilman; Kirkwood M. Land. 2020. "Antifungal Drug Repurposing." Antibiotics 9, no. 11: 812.
Plant-derived anthraquinones were evaluated in cell assays for their inhibitory activities against the parasitic protozoa Trichomonas vaginalis human strain G3 that causes the sexually transmitted disease trichomoniasis in women, Tritrichomonas foetus bovine strain D1 that causes sexually transmitted diseases in farm animals (bulls, cows, and pigs), Tritrichomonas foetus-like strain C1 that causes diarrhea in domestic animals (cats and dogs), and bacteria and fungi. The anthraquinones assessed for their inhibitory activity were anthraquinone, aloe-emodin (1,8-dihydroxy-3-hydroxymethylanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), chrysazin (1,8-dihydroxyanthraquinone), emodin (1,3,8-trihydroxy-6-methylanthraquinone), purpurin (1,2,4-trihydroxyanthraquinone), and rhein (1,8-dihydroxy-3-carboxyanthraquinone). Their activities were determined in terms of IC50 values, defined as the concentration that inhibits 50% of the cells under the test conditions and calculated from linear dose response plots for the parasitic protozoa, and zone of inhibition for bacteria and fungi, respectively. The results show that the different substituents on the anthraquinone ring seem to influence the relative potency. Analysis of the structure–activity relationships in protozoa indicates that the aloe-emodin and chrysazin with the highest biological activities merit further study for their potential to help treat the diseases in women and domestic and farm animals. Emodin also exhibited antifungal activity against Candida albicans. The suggested mechanism of action and the additional reported beneficial biological properties of anthraquinones suggest that they have the potential to ameliorate a broad spectrum of human diseases.
Mendel Friedman; Alexander Xu; Rani Lee; Daniel N. Nguyen; Tina A. Phan; Sabrina M. Hamada; Rima Panchel; Christina C. Tam; Jong H. Kim; Luisa W. Cheng; Kirkwood M. Land. The Inhibitory Activity of Anthraquinones against Pathogenic Protozoa, Bacteria, and Fungi and the Relationship to Structure. Molecules 2020, 25, 3101 .
AMA StyleMendel Friedman, Alexander Xu, Rani Lee, Daniel N. Nguyen, Tina A. Phan, Sabrina M. Hamada, Rima Panchel, Christina C. Tam, Jong H. Kim, Luisa W. Cheng, Kirkwood M. Land. The Inhibitory Activity of Anthraquinones against Pathogenic Protozoa, Bacteria, and Fungi and the Relationship to Structure. Molecules. 2020; 25 (13):3101.
Chicago/Turabian StyleMendel Friedman; Alexander Xu; Rani Lee; Daniel N. Nguyen; Tina A. Phan; Sabrina M. Hamada; Rima Panchel; Christina C. Tam; Jong H. Kim; Luisa W. Cheng; Kirkwood M. Land. 2020. "The Inhibitory Activity of Anthraquinones against Pathogenic Protozoa, Bacteria, and Fungi and the Relationship to Structure." Molecules 25, no. 13: 3101.
The mushroom poison that causes the most deaths is the class of toxins known as amatoxins. Current methods to sensitively and selectively detect these toxins are limited by the need for expensive equipment, or they lack accuracy due to cross-reactivity with other chemicals found in mushrooms. In this work, we report the development of a competition-based lateral flow immunoassay (LFIA) for the rapid, portable, selective, and sensitive detection of amatoxins. Our assay clearly indicates the presence of 10 ng/mL of α-AMA or γ-AMA and the method including extraction and detection can be completed in approximately 10 minutes. The test can be easily read by eye and has a presumed shelf-life of at least 1 year. From testing 110 wild mushrooms, the LFIA identified 6 out of 6 species that were known to contain amatoxins. Other poisonous mushrooms known not to contain amatoxins tested negative by LFIA. This LFIA can be used to quickly identify amatoxin-containing mushrooms.
Candace S. Bever; Catharine A. Adams; Robert M. Hnasko; Luisa W. Cheng; Larry H. Stanker. Lateral flow immunoassay (LFIA) for the detection of lethal amatoxins from mushrooms. PLOS ONE 2020, 15, e0231781 .
AMA StyleCandace S. Bever, Catharine A. Adams, Robert M. Hnasko, Luisa W. Cheng, Larry H. Stanker. Lateral flow immunoassay (LFIA) for the detection of lethal amatoxins from mushrooms. PLOS ONE. 2020; 15 (4):e0231781.
Chicago/Turabian StyleCandace S. Bever; Catharine A. Adams; Robert M. Hnasko; Luisa W. Cheng; Larry H. Stanker. 2020. "Lateral flow immunoassay (LFIA) for the detection of lethal amatoxins from mushrooms." PLOS ONE 15, no. 4: e0231781.
Bacterial pathogens have developed exquisite virulence mechanisms to survive in the host cells. These virulence mechanisms help them bind and internalize into host cells, replicate, and evade the host immune response. The mammalian host itself has developed its own repertoire of weapons to prevent this from happening. One important component of host response in preventing infections in the gut lumen is the diverse commensal microbiota present. Dysbiosis of the gut microbiota has been implicated in the development of many gastrointestinal diseases. A potential therapeutic pathway to solve these diseases would be by providing probiotics and/or prebiotics to help stimulate growth of the beneficial commensal bacteria. Here, we will present evidence of commensal microbiota imbalance in the development of disease as well as potential therapies to restore gut harmony.
Christina C. Tam; Kirkwood M. Land; Luisa W. Cheng. Prebiotics, Probiotics, and Bacterial Infections. Prebiotics and Probiotics - Potential Benefits in Nutrition and Health 2020, 1 .
AMA StyleChristina C. Tam, Kirkwood M. Land, Luisa W. Cheng. Prebiotics, Probiotics, and Bacterial Infections. Prebiotics and Probiotics - Potential Benefits in Nutrition and Health. 2020; ():1.
Chicago/Turabian StyleChristina C. Tam; Kirkwood M. Land; Luisa W. Cheng. 2020. "Prebiotics, Probiotics, and Bacterial Infections." Prebiotics and Probiotics - Potential Benefits in Nutrition and Health , no. : 1.
Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of α-amanitin (α-AMA) or γ-AMA, and 100 ng/mL of β-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography–mass spectrometry (LC-MS) methods.
Candace S. Bever; Kenneth D. Swanson; Elizabeth I. Hamelin; Michael Filigenzi; Robert H. Poppenga; Jennifer Kaae; Luisa W. Cheng; Larry H. Stanker. Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine. Toxins 2020, 12, 123 .
AMA StyleCandace S. Bever, Kenneth D. Swanson, Elizabeth I. Hamelin, Michael Filigenzi, Robert H. Poppenga, Jennifer Kaae, Luisa W. Cheng, Larry H. Stanker. Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine. Toxins. 2020; 12 (2):123.
Chicago/Turabian StyleCandace S. Bever; Kenneth D. Swanson; Elizabeth I. Hamelin; Michael Filigenzi; Robert H. Poppenga; Jennifer Kaae; Luisa W. Cheng; Larry H. Stanker. 2020. "Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine." Toxins 12, no. 2: 123.
Contamination of foods or environments by fungi, especially those resistant to conventional fungicides or drugs, represents a hazard to human health. The objective of this study is to identify safe, natural antifungal agents that can rapidly remove fungal pathogens or contaminants from food and/or environmental sources. Fifteen antifungal compounds (nine benzo derivatives as candidates; six conventional fungicides as references) were investigated. Three benzo analogs, namely, octyl gallate (OG), trans-cinnamaldehyde (CA) and 2-hydroxy-5-methoxybenzaldehyde (2H5M), at 1 g L-1 (3.54 mmol), 1 mL L-1 (7.21 mmol), 1 mL L-1 (5.39 mmol), respectively, achieved ≥ 99.9% fungal death after 0.5, 2.5 or 24 h of treatments, respectively, in in vitro phosphate buffered saline (PBS) bioassay. However, when OG, CA and 2H5M were examined in commercial food matrices, organic apple or grape juices, only CA maintained a similar level of antifungal activity, compared to a PBS bioassay. CA showed higher antifungal activity at pH 3.5, equivalent to that of commercial fruit juices, than at pH 5.6. In soil sample tests, application of 1 mL L-1 (7.21 mmol) CA to conventional maize/tomato soil samples (pH 6.8) for 2.5 h resulted in ≥ 99.9% fungal death, indicating CA could also eliminate fungal contaminants in soil. While the conventional fungicide thiabendazole exerted antifungal activity comparable to CA, thiabendazole enhanced the production of carcinogenic aflatoxins by Aspergillus flavus, an undesirable side-effect. CA could be developed as a potent antifungal agent in food processing or soil sanitation by reducing time/costs necessary for fungal removal. This article is protected by copyright. All rights reserved.
Jong H. Kim; Kathleen L. Chan; Noreen Mahoney; Luisa W. Cheng; Nicole Tautges; Kate Scow. Rapid elimination of foodborne and environmental fungal contaminants by benzo analogs. Journal of the Science of Food and Agriculture 2020, 100, 2800 -2806.
AMA StyleJong H. Kim, Kathleen L. Chan, Noreen Mahoney, Luisa W. Cheng, Nicole Tautges, Kate Scow. Rapid elimination of foodborne and environmental fungal contaminants by benzo analogs. Journal of the Science of Food and Agriculture. 2020; 100 (6):2800-2806.
Chicago/Turabian StyleJong H. Kim; Kathleen L. Chan; Noreen Mahoney; Luisa W. Cheng; Nicole Tautges; Kate Scow. 2020. "Rapid elimination of foodborne and environmental fungal contaminants by benzo analogs." Journal of the Science of Food and Agriculture 100, no. 6: 2800-2806.
Background: Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the C-terminus to BoNT/A and neutralization studies. The purpose of this study was to define the immunologic identity of the novel BoNT. Methods: monoclonal antibodies (mAbs) to the novel BoNT/H N-terminus were generated by antibody repertoire cloning and yeast display after immunization with BoNT/H LC-HN or BoNT/F LC-HN. Results: 21 unique BoNT/H LC-HN mAbs were obtained; 15 from the BoNT/H LC-HN immunized library (KD 0.78 nM to 182 nM) and six from the BoNT/F-immunized libraries (KD 20.5 nM to 1490 nM). A total of 15 of 21 mAbs also bound catalytically inactive BoNT/H holotoxin. The mAbs bound nine non-overlapping epitopes on the BoNT/H LC-HN. None of the mAbs showed binding to BoNT serotypes A-G, nor any of the seven subtypes of BoNT/F, except for one mAb that weakly bound BoNT/F5. Conclusions: The results, combined with the chimeric structure and neutralization by anti-A, but not anti-F antitoxin indicate that immunologically the novel BoNT is BoNT/HA. This determination has significant implications for existing countermeasures and potential vulnerabilities.
Yongfeng Fan; Jason R. Barash; Fraser Conrad; Jianlong Lou; Christina Tam; Luisa W. Cheng; Stephen S. Arnon; James D. Marks. The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA. Toxins 2019, 12, 9 .
AMA StyleYongfeng Fan, Jason R. Barash, Fraser Conrad, Jianlong Lou, Christina Tam, Luisa W. Cheng, Stephen S. Arnon, James D. Marks. The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA. Toxins. 2019; 12 (1):9.
Chicago/Turabian StyleYongfeng Fan; Jason R. Barash; Fraser Conrad; Jianlong Lou; Christina Tam; Luisa W. Cheng; Stephen S. Arnon; James D. Marks. 2019. "The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA." Toxins 12, no. 1: 9.
Amatoxins (AMAs) are lethal toxins found in a variety of mushroom species. Detection methods are needed to determine the occurrence of AMAs in mushroom species suspected in mushroom poisonings. In this manuscript, we report the generation of novel monoclonal antibodies (mAbs, AMA9G3 and AMA9C12) and the development of a competitive, enzyme-linked immunosorbent assay (cELISA) that is sensitive at 1 ng mL−1 and shows selectivity for α-amanitin (α-AMA) and γ-amanitin (γ-AMA), and less for β-amanitin (β-AMA). In order to decrease the overall time needed for analysis, the extraction procedure for mushrooms was also simplified. A rapid (1 min) extraction procedure of AMAs using solvents as simple as water alone was successfully demonstrated using Amanita mushrooms. Together, the extraction method and the mAb-based ELISA represent a simple and rapid method that readily detects AMAs extracted from mushroom samples.
Candace S. Bever; Robert M. Hnasko; Luisa W. Cheng; Larry H. Stanker. A Rapid Extraction Method Combined with a Monoclonal Antibody-Based Immunoassay for the Detection of Amatoxins. Toxins 2019, 11, 724 .
AMA StyleCandace S. Bever, Robert M. Hnasko, Luisa W. Cheng, Larry H. Stanker. A Rapid Extraction Method Combined with a Monoclonal Antibody-Based Immunoassay for the Detection of Amatoxins. Toxins. 2019; 11 (12):724.
Chicago/Turabian StyleCandace S. Bever; Robert M. Hnasko; Luisa W. Cheng; Larry H. Stanker. 2019. "A Rapid Extraction Method Combined with a Monoclonal Antibody-Based Immunoassay for the Detection of Amatoxins." Toxins 11, no. 12: 724.
This study examined the anti-protozoal effects of selected benzo derivatives, namely ten gallic acid (GA) alkyl esters (viz., benzoic acid analogs) and twenty-three benzaldehyde analogs, against six different anaerobic human protozoal pathogens- - Trichomonas vaginalis, Tritrichomonas foetus, Tritrichomonas foetus-like, Giardia lamblia, Entamoeba histolytica, and Naegleria fowleri. The efficacy of benzaldehyde and gallate (3,4,5-trihydroxybenzoic acid) analogs were investigated in two respects: (1) changing types of side chains and their positions on the benzaldehyde ring [structure–activity relationships (SAR)]; and, (2) changing lengths of alkyl chains esterified with the carboxyl group on gallate. Results of parasite growth inhibition assays indicated that benzo derivatives could be further developed as potent anti-protozoal drug candidates/leads, where GA having longer alkyl chains exhibited higher anti-protozoal activity than compounds with shorter alkyl chains or all benzaldehyde analogs tested. The chemical libraries were also screened against common human microbiome bacteria and no detectable inhibition was observed. Structure-activity relationships and their implications for new drug discovery against these sexually-transmitted, water-borne, and food- borne parasites are discussed.
Kirkwood Land; Jong Kim; Vincent Huang; Hye Hahn; Anjan Debnath; Christina Tam; Luisa Cheng. Repurposing Common Food Additives (Benzo Derivatives) As New Anti-parasitic Agents. Proceedings of 5th International Electronic Conference on Medicinal Chemistry 2019, 1 .
AMA StyleKirkwood Land, Jong Kim, Vincent Huang, Hye Hahn, Anjan Debnath, Christina Tam, Luisa Cheng. Repurposing Common Food Additives (Benzo Derivatives) As New Anti-parasitic Agents. Proceedings of 5th International Electronic Conference on Medicinal Chemistry. 2019; ():1.
Chicago/Turabian StyleKirkwood Land; Jong Kim; Vincent Huang; Hye Hahn; Anjan Debnath; Christina Tam; Luisa Cheng. 2019. "Repurposing Common Food Additives (Benzo Derivatives) As New Anti-parasitic Agents." Proceedings of 5th International Electronic Conference on Medicinal Chemistry , no. : 1.
Botulism is a devastating disease caused by botulinum neurotoxins (BoNTs) secreted primarily by Clostridium botulinum. Mouse bioassays without co-inoculation with antibodies are the standard method for the detection of BoNTs, but are not capable of distinguishing between the different serotypes (A–G). Most foodborne intoxications are caused by serotypes BoNT/A and BoNT/B. BoNT/E outbreaks are most often observed in northern coastal regions and are associated with eating contaminated marine animals and other fishery products. Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of BoNT/E3. Monoclonal antibodies (mAbs) were generated against BoNT/E3 by immunizing with recombinant peptide fragments of the light and heavy chains of BoNT/E3. In all, 12 mAbs where characterized for binding to both the recombinant peptides and holotoxin, as well as their performance in Western blots and sandwich ELISAs. The most sensitive sandwich assay, using different mAbs for capture and detection, exhibited a limit of detection of 0.2 ng/ml in standard buffer matrix and 10 ng/mL in fish product matrices. By employing two different mAbs for capture and detection, a more standardized sandwich assay was constructed. Development of sensitive and selective mAbs to BoNT/E would help in the initial screening of potential food contamination, speeding diagnosis and reducing use of laboratory animals.
Candace S. Bever; Miles Scotcher; Luisa W. Cheng; Robert M. Hnasko; Larry H. Stanker. Development and Characterization of Monoclonal Antibodies to Botulinum Neurotoxin Type E. Toxins 2019, 11, 407 .
AMA StyleCandace S. Bever, Miles Scotcher, Luisa W. Cheng, Robert M. Hnasko, Larry H. Stanker. Development and Characterization of Monoclonal Antibodies to Botulinum Neurotoxin Type E. Toxins. 2019; 11 (7):407.
Chicago/Turabian StyleCandace S. Bever; Miles Scotcher; Luisa W. Cheng; Robert M. Hnasko; Larry H. Stanker. 2019. "Development and Characterization of Monoclonal Antibodies to Botulinum Neurotoxin Type E." Toxins 11, no. 7: 407.
Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated "chemosensitization" as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen Aspergillus fumigatus. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.
Jong H. Kim; Kathleen L. Chan; Luisa W. Cheng; Lisa A. Tell; Barbara A. Byrne; Kristin Clothier; Kirkwood M. Land. High Efficiency Drug Repurposing Design for New Antifungal Agents. Methods and Protocols 2019, 2, 31 .
AMA StyleJong H. Kim, Kathleen L. Chan, Luisa W. Cheng, Lisa A. Tell, Barbara A. Byrne, Kristin Clothier, Kirkwood M. Land. High Efficiency Drug Repurposing Design for New Antifungal Agents. Methods and Protocols. 2019; 2 (2):31.
Chicago/Turabian StyleJong H. Kim; Kathleen L. Chan; Luisa W. Cheng; Lisa A. Tell; Barbara A. Byrne; Kristin Clothier; Kirkwood M. Land. 2019. "High Efficiency Drug Repurposing Design for New Antifungal Agents." Methods and Protocols 2, no. 2: 31.
Abrin, a highly toxic plant toxin, is a potential bioterror weapon. Work from our laboratory and others have shown that abrin is highly resistant to both thermal and pH inactivation methods. We sought to evaluate the effectiveness of selected food processing thermal inactivation conditions against abrin in economically important food matrices (whole milk, non-fat milk, liquid egg, and ground beef). The effectiveness of toxin inactivation was measured via three different assays: (1) In vitro cell free translation (CFT) assay, (2) Vero cell culture cytotoxicity; and the in vivo mouse intraperitoneal (ip) bioassay. For both whole and non-fat milk, complete inactivation was achieved at temperatures of ≥ 80 °C for 3 min or 134 °C for 60 s, which were higher than the normal vat/batch pasteurization or the high temperature short time pasteurization (HTST). Toxin inactivation in liquid egg required temperatures of ≥ 74 °C for 3 min higher than suggested temperatures for scrambled eggs (22% solids) and plain whole egg. Additionally, the ground beef (80:20%) matrix was found to be inhibitory for full toxin activity in the mouse bioassay while retaining some activity in both the cell free translation assay and Vero cell culture cytotoxicity assay.
Christina C. Tam; Thomas D. Henderson; Larry H. Stanker; Luisa W. Cheng. Influence of Food Matrices on the Stability and Bioavailability of Abrin. Toxins 2018, 10, 502 .
AMA StyleChristina C. Tam, Thomas D. Henderson, Larry H. Stanker, Luisa W. Cheng. Influence of Food Matrices on the Stability and Bioavailability of Abrin. Toxins. 2018; 10 (12):502.
Chicago/Turabian StyleChristina C. Tam; Thomas D. Henderson; Larry H. Stanker; Luisa W. Cheng. 2018. "Influence of Food Matrices on the Stability and Bioavailability of Abrin." Toxins 10, no. 12: 502.
Botulinum neurotoxin (BoNT) intoxication can lead to the disease botulism, characterized by flaccid muscle paralysis that can cause respiratory failure and death. Due to the significant morbidity and mortality costs associated with BoNTs high toxicity, developing highly sensitive, rapid, and field-deployable assays are critically important to protect the nation’s food supply against either accidental or intentional contamination. We report here that the B-cell based biosensor assay CANARY® (Cellular Analysis and Notification of Antigen Risks and Yields) Zephyr detects BoNT/A holotoxin at limits of detection (LOD) of 10.0 ± 2.5 ng/mL in assay buffer. Milk matrices (whole milk, 2% milk and non-fat milk) with BoNT/A holotoxin were detected at similar levels (7.4–7.9 ng/mL). BoNT/A complex was positive in carrot, orange, and apple juices at LODs of 32.5–75.0 ng/mL. The detection of BoNT/A complex in solid complex foods (ground beef, smoked salmon, green bean baby puree) ranged from 14.8 ng/mL to 62.5 ng/mL. Detection of BoNT/A complex in the viscous liquid egg matrix required dilution in assay buffer and gave a LOD of 171.9 ± 64.7 ng/mL. These results show that the CANARY® Zephyr assay can be a highly useful qualitative tool in environmental and food safety surveillance programs.
Christina C. Tam; Andrew R. Flannery; Luisa W. Cheng. A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices. Toxins 2018, 10, 476 .
AMA StyleChristina C. Tam, Andrew R. Flannery, Luisa W. Cheng. A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices. Toxins. 2018; 10 (11):476.
Chicago/Turabian StyleChristina C. Tam; Andrew R. Flannery; Luisa W. Cheng. 2018. "A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices." Toxins 10, no. 11: 476.
There has been a persistent effort to improve efficacy of conventional antimycotic drugs. However, current antimycotic interventions have often limited efficiency in treating fungal pathogens, especially those resistant to drugs. Considering development of entirely new antimycotic drugs is a capital-intensive and time-consuming process, we investigated an alternative approach termed drug repurposing whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antimycotic agents. As a proof of concept, we applied chemosensitization as a new screening strategy, where combined application of a second compound, viz., chemosensitizer, with a conventional drug could enhance antifungal efficacy of the drug co-applied. Unlike the conventional combination therapy, a chemosensitizer itself does not necessarily have to possess an antifungal activity, but the chemosensitizer significantly debilitates defense systems of pathogens to drugs, enabling improved identification of antifungal activity of off-patent drugs. Of note, inclusion of fungal mutants, such as antioxidant mutants, could facilitate drug repurposing process by enhancing the sensitivity of antifungal screening. Altogether, our strategy could lead to high efficiency drug repurposing, which enhances the drug susceptibility of targeted fungal pathogens.
Jong H. Kim; Kathleen L. Chan; Luisa W. Cheng; Lisa A. Tell; Barbara A. Byrne; Kristin Clothier; Kirkwood M. Land. High Efficiency Drug Repurposing for New Antifungal Agents. Proceedings of 4th International Electronic Conference on Medicinal Chemistry 2018, 1 .
AMA StyleJong H. Kim, Kathleen L. Chan, Luisa W. Cheng, Lisa A. Tell, Barbara A. Byrne, Kristin Clothier, Kirkwood M. Land. High Efficiency Drug Repurposing for New Antifungal Agents. Proceedings of 4th International Electronic Conference on Medicinal Chemistry. 2018; ():1.
Chicago/Turabian StyleJong H. Kim; Kathleen L. Chan; Luisa W. Cheng; Lisa A. Tell; Barbara A. Byrne; Kristin Clothier; Kirkwood M. Land. 2018. "High Efficiency Drug Repurposing for New Antifungal Agents." Proceedings of 4th International Electronic Conference on Medicinal Chemistry , no. : 1.
Botulinum neurotoxin (BoNT) intoxication can lead to the disease botulism, characterized by flaccid muscle paralysis that can cause respiratory failure and death. Due to the significant morbidity and mortality costs associated with BoNTs high toxicity, developing highly sensitive, rapid, and field-deployable assays are critically important to protect the nation’s food supply against either accidental or intentional contamination. We report here that the B-cell based biosensor assay (CANARY® Zephyr) detects BoNT/A in buffer and various food matrices rapidly in ≤ 40 min, in small volumes ≈ 50 μL, with minimal processing of samples, and is extremely portable (suitcase-sized equipment). BoNT/A was detected at limits of detection (LOD) < 0.075 ng ± 0.02 in assay buffer while milk matrices (non-fat, 2 %, whole milk) increased the LOD to < 0.175 – 0.314 ng. Limits of detection for the assay in complex foods were < 1 ng ± 0.0 (neutralized acidic juices-carrot, orange and apple); < 16.7 ng ± 7.7 (liquid egg); and varied from < 0. 39 – 3.125 ng for solid complex foods (ground beef, green bean baby puree, smoked salmon). These results show that the CANARY® Zephyr assay can be a highly useful tool in clinical, environmental, and food safety surveillance programs.
Christina C. Tam; Andrew R. Flannery; Luisa W. Cheng. A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices. 2018, 1 .
AMA StyleChristina C. Tam, Andrew R. Flannery, Luisa W. Cheng. A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices. . 2018; ():1.
Chicago/Turabian StyleChristina C. Tam; Andrew R. Flannery; Luisa W. Cheng. 2018. "A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices." , no. : 1.
Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.
Maureen Gumbo; Richard M. Beteck; Tawanda Mandizvo; Ronnett Seldon; Digby F. Warner; Heinrich C. Hoppe; Michelle Isaacs; Dustin Laming; Christina C. Tam; Luisa W. Cheng; Nicole Liu; Kirkwood M. Land; Setshaba D. Khanye. Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity. Molecules 2018, 23, 2038 .
AMA StyleMaureen Gumbo, Richard M. Beteck, Tawanda Mandizvo, Ronnett Seldon, Digby F. Warner, Heinrich C. Hoppe, Michelle Isaacs, Dustin Laming, Christina C. Tam, Luisa W. Cheng, Nicole Liu, Kirkwood M. Land, Setshaba D. Khanye. Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity. Molecules. 2018; 23 (8):2038.
Chicago/Turabian StyleMaureen Gumbo; Richard M. Beteck; Tawanda Mandizvo; Ronnett Seldon; Digby F. Warner; Heinrich C. Hoppe; Michelle Isaacs; Dustin Laming; Christina C. Tam; Luisa W. Cheng; Nicole Liu; Kirkwood M. Land; Setshaba D. Khanye. 2018. "Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity." Molecules 23, no. 8: 2038.
Prinessa Chellan; Vicky M. Avery; Sandra Duffy; James A. Triccas; Gayathri Nagalingam; Christina Tam; Luisa W. Cheng; Jenny Liu; Kirkwood M. Land; Guy J. Clarkson; Isolda Romero-Canelón; Peter J. Sadler. Frontispiece: Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance. Chemistry – A European Journal 2018, 24, 1 .
AMA StylePrinessa Chellan, Vicky M. Avery, Sandra Duffy, James A. Triccas, Gayathri Nagalingam, Christina Tam, Luisa W. Cheng, Jenny Liu, Kirkwood M. Land, Guy J. Clarkson, Isolda Romero-Canelón, Peter J. Sadler. Frontispiece: Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance. Chemistry – A European Journal. 2018; 24 (40):1.
Chicago/Turabian StylePrinessa Chellan; Vicky M. Avery; Sandra Duffy; James A. Triccas; Gayathri Nagalingam; Christina Tam; Luisa W. Cheng; Jenny Liu; Kirkwood M. Land; Guy J. Clarkson; Isolda Romero-Canelón; Peter J. Sadler. 2018. "Frontispiece: Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance." Chemistry – A European Journal 24, no. 40: 1.
One of the deadliest mushrooms is the death cap mushroom, Amanita phalloides. The most toxic constituent is α-amanitin, a bicyclic octapeptide, which damages the liver and kidneys. To develop a new tool for detecting this toxin, polyclonal antibodies were generated and characterized. Both α- and β-amanitin were coupled to carrier proteins through four different linking chemistries, one of which has never before been described. These conjugates were evaluated for their effectiveness in generating antibodies specific for the free toxin, as well as their utility in formatting heterogeneous assays with high sensitivity. Ultimately, these efforts yielded a newly described conjugation procedure utilizing periodate oxidation followed by reductive amination that successfully resulted in generating sensitive immunoassays (limit of detection (LOD), ~1.0 µg/L). The assays were characterized for their selectivity and were found to equally detect α-, β-, and γ-amanitin, and not cross-react with other toxins tested. Toxin detection in mushrooms was possible using a simple sample preparation method. This enzyme-linked immunosorbent assay (ELISA) is a simple and fast test, and readily detects amatoxins extracted from A. phalloides.
Candace S. Bever; Bogdan Barnych; Robert Hnasko; Luisa W. Cheng; Larry H. Stanker. A New Conjugation Method Used for the Development of an Immunoassay for the Detection of Amanitin, a Deadly Mushroom Toxin. Toxins 2018, 10, 265 .
AMA StyleCandace S. Bever, Bogdan Barnych, Robert Hnasko, Luisa W. Cheng, Larry H. Stanker. A New Conjugation Method Used for the Development of an Immunoassay for the Detection of Amanitin, a Deadly Mushroom Toxin. Toxins. 2018; 10 (7):265.
Chicago/Turabian StyleCandace S. Bever; Bogdan Barnych; Robert Hnasko; Luisa W. Cheng; Larry H. Stanker. 2018. "A New Conjugation Method Used for the Development of an Immunoassay for the Detection of Amanitin, a Deadly Mushroom Toxin." Toxins 10, no. 7: 265.
Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N,N'‐chelated pyridylimino‐ or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by x‐ray crystallography. Rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10 ‐ 2.0 µM in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes), but were only moderately active towards Trichomonas vaginalis. They were active in both the asexual blood stage and the sexual late stage gametocyte assays, whereas the clinical parent drug, sulfadoxine, was inactive. Five complexes were moderately active against Mycobacterium tuberculosis (IC50 < 6.3 µM), whereas sulfadoxine showed no antitubercular activity. An increase in the size of both the Cpx ligand and the aromatic imino substituent increased hydrophobicity, which resulted in an increase in antiplasmodial activity.
Prinessa Chellan; Vicky M. Avery; Sandra Duffy; James A. Triccas; Gayathri Nagalingam; Christina Tam; Luisa W. Cheng; Jenny Liu; Kirkwood M. Land; Guy J. Clarkson; Isolda Romero‐Canelón; Peter J. Sadler. Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance. Chemistry – A European Journal 2018, 24, 10078 -10090.
AMA StylePrinessa Chellan, Vicky M. Avery, Sandra Duffy, James A. Triccas, Gayathri Nagalingam, Christina Tam, Luisa W. Cheng, Jenny Liu, Kirkwood M. Land, Guy J. Clarkson, Isolda Romero‐Canelón, Peter J. Sadler. Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance. Chemistry – A European Journal. 2018; 24 (40):10078-10090.
Chicago/Turabian StylePrinessa Chellan; Vicky M. Avery; Sandra Duffy; James A. Triccas; Gayathri Nagalingam; Christina Tam; Luisa W. Cheng; Jenny Liu; Kirkwood M. Land; Guy J. Clarkson; Isolda Romero‐Canelón; Peter J. Sadler. 2018. "Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance." Chemistry – A European Journal 24, no. 40: 10078-10090.