scholarly journals Anti-Virulence Properties of Plant Species: Correlation between In Vitro Activity and Efficacy in a Murine Model of Bacterial Infection

2021 ◽  
Vol 9 (12) ◽  
pp. 2424
Author(s):  
José Luis Díaz-Núñez ◽  
Macrina Pérez-López ◽  
Norma Espinosa ◽  
Nayelli Campos-Hernández ◽  
Rodolfo García-Contreras ◽  
...  
Keyword(s):  
Plant Extracts ◽  
Murine Model ◽  
Type Iii Secretion ◽  
Virulence Determinants ◽  
Mutant Strains ◽  
Bacterial Quorum Sensing ◽  
Bacterial Quorum ◽  
Virulence Properties

Several plant extracts exhibit anti-virulence properties due to the interruption of bacterial quorum sensing (QS). However, studies on their effects at the preclinical level are scarce. Here, we used a murine model of abscess/necrosis induced by Pseudomonas aeruginosa to evaluate the anti-pathogenic efficacy of 24 plant extracts at a sub-inhibitory concentration. We analyzed their ability to inhibit QS-regulated virulence factors such as swarming, pyocyanin production, and secretion of the ExoU toxin via the type III secretion system (T3SS). Five of the seven extracts with the best anti-pathogenic activity reduced ExoU secretion, and the extracts of Diphysa americana and Hibiscus sabdariffa were identified as the most active. Therefore, the abscess/necrosis model allows identification of plant extracts that have the capacity to reduce pathogenicity of P. aeruginosa. Furthermore, we evaluated the activity of the plant extracts on Chromobacterium violaceum. T3SS (ΔescU) and QS (ΔcviI) mutant strains were assessed in both the abscess/necrosis and sepsis models. Only the ΔescU strain had lower pathogenicity in the animal models, although no activity of plant extracts was observed. These results demonstrate differences between the anti-virulence activity recorded in vitro and pathogenicity in vivo and between the roles of QS and T3S systems as virulence determinants.

scholarly journals Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1503
Author(s):  
Carla Guijarro-Real ◽  
Mariola Plazas ◽  
Adrián Rodríguez-Burruezo ◽  
Jaime Prohens ◽  
Ana Fita
Keyword(s):  
Plant Extracts ◽  
Curcuma Longa ◽  
Hydrolysis Product ◽  
Resonance Energy ◽  
Significant Inhibition ◽  
Main Role ◽  
Turmeric Extract ◽  
Ic50 Value

Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CLPro) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CLPro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CLPro activity using a quenched fluorescence resonance energy transfer (FRET) assay. Extracts from turmeric (Curcuma longa) rhizomes, mustard (Brassica nigra) seeds, and wall rocket (Diplotaxis erucoides subsp. erucoides) at 500 µg mL−1 displayed significant inhibition of the 3CLPro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively. Using different extract concentrations, an IC50 value of 15.74 µg mL−1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CLPro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract must also play a main role in inhibiting the 3CLPro activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CLPro inhibitory activity; however, its hydrolysis product allyl isothiocyanate had an IC50 value of 41.43 µg mL−1. The current study identifies plant extracts and molecules that can be of interest in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials.

scholarly journals Preclinical Studies in Anti-Trypanosomatidae Drug Development

2021 ◽  
Vol 14 (7) ◽  
pp. 644
Author(s):  
Cintya Perdomo ◽  
Elena Aguilera ◽  
Ileana Corvo ◽  
Paula Faral-Tello ◽  
Elva Serna ◽  
...  
Keyword(s):  
Rural Communities ◽  
Chagas Disease ◽  
Murine Model ◽  
Mammalian Cells ◽  
Drug Candidate ◽  
Murine Macrophages ◽  
Causative Agents ◽  
Trypanosomatid Parasites

The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic. In our search for novel anti-trypanosomatid agents, we assess the growth-inhibitory properties of >450 compounds from in-house and/or “Pathogen Box” (PBox) libraries against L. infantum, L. amazonensis, L.braziliensis, T. cruzi and T. brucei and evaluate the toxicities of the most promising agents towards murine macrophages. Screens using the in-house series identified 17 structures with activity against and selective toward Leishmania: Compounds displayed 50% inhibitory concentrations between 0.09 and 25 μM and had selectivity index values >10. For the PBox library, ~20% of chemicals exhibited anti-parasitic properties including five structures whose activity against L. infantum had not been reported before. These five compounds displayed no toxicity towards murine macrophages over the range tested with three being active in an in vivo murine model of the cutaneous disease, with 100% survival of infected animals. Additionally, the oral combination of three of them in the in vivo Chagas disease murine model demonstrated full control of the parasitemia. Interestingly, phenotyping revealed that the reference strain responds differently to the five PBox-derived chemicals relative to parasites isolated from a dog. Together, our data identified one drug candidate that displays activity against Leishmania and other Trypanosomatidae in vitro and in vivo, while exhibiting low toxicity to cultured mammalian cells and low in vivo acute toxicity.

scholarly journals Evidence for the Involvement of the Glc7-Reg1 Phosphatase and the Snf1-Snf4 Kinase in the Regulation of INO1 Transcription in Saccharomyces cerevisiae

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 73-87 ◽  
Author(s):  
Margaret K Shirra ◽  
Karen M Arndt
Keyword(s):  
Rna Polymerase Ii ◽  
Glucose Repression ◽  
Snf1 Kinase ◽  
Glucose Levels ◽  
Recessive Mutations ◽  
Mutant Strains ◽  
Rna Polymerase Ii Transcription ◽  
Two Hybrid

AbstractBinding of the TATA-binding protein (TBP) to the promoter is a pivotal step in RNA polymerase II transcription. To identify factors that regulate TBP, we selected for suppressors of a TBP mutant that exhibits promoter-specific defects in activated transcription in vivo and severely reduced affinity for TATA boxes in vitro. Dominant mutations in SNF4 and recessive mutations in REG1, OPI1, and RTF2 were isolated that specifically suppress the inositol auxotrophy of the TBP mutant strains. OPI1 encodes a repressor of INO1 transcription. REG1 and SNF4 encode regulators of the Glc7 phosphatase and Snf1 kinase, respectively, and have well-studied roles in glucose repression. In two-hybrid assays, one SNF4 mutation enhances the interaction between Snf4 and Snf1. Suppression of the TBP mutant by our reg1 and SNF4 mutations appears unrelated to glucose repression, since these mutations do not alleviate repression of SUC2, and glucose levels have little effect on INO1 transcription. Moreover, mutations in TUP1, SSN6, and GLC7, but not HXK2 and MIG1, can cause suppression. Our data suggest that association of TBP with the TATA box may be regulated, directly or indirectly, by a substrate of Snf1. Analysis of INO1 transcription in various mutant strains suggests that this substrate is distinct from Opi1.

scholarly journals Sulfated poly-amido-saccharides (sulPASs) are anticoagulants in vitro and in vivo

2021 ◽  
Vol 12 (38) ◽  
pp. 12719-12725
Author(s):  
Maria Varghese ◽  
Rae S. Rokosh ◽  
Carolyn A. Haller ◽  
Stacy L. Chin ◽  
Jiaxuan Chen ◽  
...  
Keyword(s):  
Murine Model ◽  
Protamine Sulfate ◽  
Clotting Time ◽  
Risk Of Bleeding ◽  
Increased Risk

Heparin mimicking sulfated poly-amido-saccharides (sulPASs) are anticoagulants resistant to heparanases and reversed by protamine sulfate. In an in vivo murine model, sulPASs extend clotting time without the increased risk of bleeding.

scholarly journals Plant Extracts and Reactive Oxygen Species as Two Counteracting Agents with Anti- and Pro-Obesity Properties

2019 ◽  
Vol 20 (18) ◽  
pp. 4556 ◽  
Author(s):  
Hanna Zielinska-Blizniewska ◽  
Przemyslaw Sitarek ◽  
Anna Merecz-Sadowska ◽  
Katarzyna Malinowska ◽  
Karolina Zajdel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Plant Extracts ◽  
Complex Disease ◽  
Reactive Oxygen ◽  
Complementary Therapy ◽  
Biologically Active ◽  
Mitochondrial Activity ◽  
Oxygen Species

Obesity is a complex disease of great public health significance worldwide: It entails several complications including diabetes mellitus type 2, cardiovascular dysfunction and hypertension, and its prevalence is increasing around the world. The pathogenesis of obesity is closely related to reactive oxygen species. The role of reactive oxygen species as regulatory factors in mitochondrial activity in obese subjects, molecules taking part in inflammation processes linked to excessive size and number of adipocytes, and as agents governing the energy balance in hypothalamus neurons has been examined. Phytotherapy is the traditional form of treating health problems using plant-derived medications. Some plant extracts are known to act as anti-obesity agents and have been screened in in vitro models based on the inhibition of lipid accumulation in 3T3-L1 cells and activity of pancreatic lipase methods and in in vivo high-fat diet-induced obesity rat/mouse models and human models. Plant products may be a good natural alternative for weight management and a source of numerous biologically-active chemicals, including antioxidant polyphenols that can counteract the oxidative stress associated with obesity. This review presents polyphenols as natural complementary therapy, and a good nutritional strategy, for treating obesity without serious side effects.

scholarly journals Biological activity from indigenous medicinal plants of Mauritius

2005 ◽  
Vol 77 (1) ◽  
pp. 41-51 ◽  
Author(s):  
A. Gurib-Fakim ◽  
H. Subratty ◽  
F. Narod ◽  
J. Govinden-Soulange ◽  
F. Mahomoodally
Keyword(s):  
Medicinal Plant ◽  
Plant Extracts ◽  
Biological Properties ◽  
Pharmacological Properties ◽  
Plant Materials ◽  
In Vivo Screening ◽  
Medicinal Plant Extracts ◽  
Minor Ailments

The Mauritian population has a long tradition in the use of ethno-medicine, and the practice is still strong, especially in the treatment of minor ailments. Such interest stems from an existing culture, and many “tisanes” are still prepared from plant materials and sold in several markets around the island.This paper will focus on the various chemical/biological screening techniques currently being used to evaluate the biological properties of medicinal plant extracts. Particular emphasis will be put on extraction and various screening for biological/pharmacological properties. Due consideration will be given to the pharmacological approaches that utilize different animal models for the in vitro and in vivo screening of medicinal plant extracts.

scholarly journals Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis

2000 ◽  
Vol 44 (8) ◽  
pp. 2081-2085 ◽  
Author(s):  
Beth A. Arthington-Skaggs ◽  
David W. Warnock ◽  
Christine J. Morrison
Keyword(s):  
Murine Model ◽  
Invasive Candidiasis ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Resistant Isolate ◽  
National Committee ◽  
Ergosterol Content ◽  
In Vitro Antifungal Susceptibility

ABSTRACT MIC end point determination for the most commonly prescribed azole antifungal drug, fluconazole, can be complicated by “trailing” growth of the organism during susceptibility testing by the National Committee for Clinical Laboratory Standards approved M27-A broth macrodilution method and its modified broth microdilution format. To address this problem, we previously developed the sterol quantitation method (SQM) for in vitro determination of fluconazole susceptibility, which measures cellular ergosterol content rather than growth inhibition after exposure to fluconazole. To determine if SQM MICs of fluconazole correlated better with in vivo outcome than M27-A MICs, we used a murine model of invasive candidiasis and analyzed the capacity of fluconazole to treat infections caused by C. albicansisolates which were trailers (M27-A MICs at 24 and 48 h, ≤1.0 and ≥64 μg/ml, respectively; SQM MIC, ≤1.0 μg/ml), as well as those which were fluconazole sensitive (M27-A and SQM MIC, ≤1.0 μg/ml) and fluconazole resistant (M27-A MIC, ≥64 μg/ml; SQM MIC, 54 μg/ml). Compared with the untreated controls, fluconazole therapy increased the survival of mice infected with a sensitive isolate and both trailing isolates but did not increase the survival of mice infected with a resistant isolate. These results indicate that the SQM is more predictive of in vivo outcome than the M27-A method for isolates that give unclear MIC end points due to trailing growth in fluconazole.

scholarly journals Transcription of Candidate Virulence Genes ofHaemophilus ducreyi during Infection of Human Volunteers

2001 ◽  
Vol 69 (3) ◽  
pp. 1483-1487 ◽  
Author(s):  
Robert E. Throm ◽  
Stanley M. Spinola
Keyword(s):  
Experimental Infection ◽  
Virulence Genes ◽  
Human Model ◽  
Specific Gene ◽  
Gene Products ◽  
Virulence Determinants ◽  
Reverse Transcription Pcr ◽  
Human Volunteers

ABSTRACT Haemophilus ducreyi expresses several putative virulence factors in vitro. Isogenic mutant-to-parent comparisons have been performed in a human model of experimental infection to examine whether specific gene products are involved in pathogenesis. Several mutants (momp, ftpA, losB, lst, cdtC, and hhdB) were as virulent as the parent in the human model, suggesting that their gene products did not play a major role in pustule formation. However, we could not exclude the possibility that the gene of interest was not expressed during the initial stages of infection. Biopsies of pustules obtained from volunteers infected with H. ducreyiwere subjected to reverse transcription-PCR. Transcripts corresponding to momp, ftpA, losB, lst, cdtB, and hhdA were expressed in vivo. In addition, transcripts for other putative virulence determinants such as ompA2, tdhA, lspA1, andlspA2 were detected in the biopsies. These results indicate that although several candidate virulence determinants are expressed during experimental infection, they do not have a major role in the initial stages of pathogenesis.

Enhanced fitness of a Helicobacter pylori babA mutant in a murine model

2021 ◽  
Author(s):  
M. Lorena Harvey ◽  
Aung Soe Lin ◽  
Lili Sun ◽  
Tatsuki Koyama ◽  
Jennifer H. B. Shuman ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane Proteins ◽  
Population Diversity ◽  
Fitness Advantage ◽  
Neutral Locus ◽  
Mutant Strains ◽  
Bacterial Fitness ◽  
H Pylori

Helicobacter pylori genomes encode >60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify hop mutant strains that exhibit altered fitness in vivo compared to fitness in vitro , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of hop mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time in vivo compared to changes detected in the populations during library passage in vitro . The control library proliferated as a relatively stable community in vitro, but there was a reduction in the population diversity of this library in vivo and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a non-selective bottleneck in vivo . We did not identify any OMP mutants exhibiting fitness defects exclusively in vivo without corresponding fitness defects in vitro . Conversely, a babA mutant exhibited a strong fitness advantage in vivo but not in vitro . These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.

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